药学学报

Type	Protein	Species	Prenyl donor	Substrate	Prenyl substitution site	Ref.
Membrane-bound UbiA type aPTs	AfUbiA	Archaeoglobus fulgidus	FPP, GPP, GGPP	PHB	C-3	[6]
	XimB	Streptomyces xiamenensis 318	FPP, GPP, GGPP	PHB	C-3	[7]
	SmPPT	Salvia miltiorrhiza Bunge	Polyprenyl-PP	PHB	C-3	[8]
	AePGT	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	AePGT4	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	AePGT6	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	MtMenA	Mycobacterium tuberculosis	FPP, polyprenyl-PP	DHNA	C-3	[10]
	BsMenA	Bacillus subtilis	FPP, GPP, GGPP, polyprenyl-PP	DHNA	C-3	[11]
	RcDT1	Rubia cordifolia L.	DMAPP	DHNA	C-3	[12]
	MmUBIAD1	Mus musculus	GGPP	Menadione	C-3	[13]
	CtHPT	Clitoria ternatea L.	PDP	HGA	C-3	[14]
	RTD1	Oryza sativa L.	PDP	HGA	C-3	[15]
	HlPT1L	Humulus lupulus L.	SDP	HGA	C-3	[16]
	HlPT2	Humulus lupulus L.	SDP	HGA	C-3	[16]
	PcPT	Petroselinum crispum (Mill.) Hill	DMAPP	Umbelliferone	C-6, C-8	[17]
	PsPT1	Pastinaca sativa L.	DMAPP	Umbelliferone	C-6	[18]
	PsPT2	Pastinaca sativa L.	DMAPP	Umbelliferone	C-8	[18]
	AsPT1	Angelica sinensis (Oliv.) Diels	DMAPP	Umbelliferone	C-6	[19]
	AsPT2	Angelica sinensis (Oliv.) Diels	DMAPP	Umbelliferone	C-8	[19]
	PpPT1	Peucedanum praeruptorum Dunn	DMAPP	Umbelliferone	C-6	[20]
	PpPT2	Peucedanum praeruptorum Dunn	DMAPP	Umbelliferone	C-8	[20]
	ClPT1	Citrus limon (L.) Burm. F.	GPP	Umbelliferone, esculetine, 5, 7-dihydroxycoumarin, 5-methoxy-7-hydroxycoumarin	C-8	[21]
	FcPT1a	Ficus carica Linn.	DMAPP	Umbelliferone, 5-methoxy-7-hydroxycoumarin	C-6	[22]
	FcPT1b	Ficus carica Linn.	DMAPP	Umbelliferone	C-6	[22]
	AcPT1	Artemisia capillaris Thunb.	DMAPP, GPP	p-Coumaric acid, ferulate, drupanin	C-3, C-5	[23]
	CpPT1	Citrus paradisi Macf.	GPP	5, 7-Dihydroxycoumarin, 5-hydroxy-7-methoxycoumarin, xanthotoxol, bergaptol, 8-hydroxybergapten	5-OH, 8-OH	[24]
	AkPT1	Angelica keiskei Koidz.	DMAPP	Bergaptol, xanthotoxol	C-5, C-8	[24]
	MePT1	Murraya exotica L.	GPP	Umbelliferone	C-6, C-8, 7-OH	[25]
	EsPT2	Epimedium sagittatum (Sieb. et Zucc.) Maxim.	DMAPP	Kaempferol, kaempferide, naringenin	C-8	[26]
	EpPT8	Epimedium pubescens Maxim.	DMAPP	Kaempferol, quercetin, apigenin	C-8	[27]
	LaPT2	Lupinus albus L.	DMAPP	Kaempferol, quercetin, fisetin, galangin, myricetin, naringenin	C-8	[28]
	AhPT1	Artocarpus heterophyllus Lam.	DMAPP	Genistein, 6-hydroxyflavone, etc.	C-6, C-5	[29]
	GuA6DT	Glycyrrhiza uralensis Fisch.	DMAPP, GPP	Apigenin, chrysin, luteolin, etc.	C-6	[30]
	GuILDT	Glycyrrhiza uralensis Fisch.	DMAPP	Naringenin chalcone, 2′, 4′-dihydroxychalcone, etc.	C-3′	[31]
	LjG6DT	Lotus corniculatus L.	DMAPP	Genistein	C-6	[32]
	GmIDT1	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	B-ring	[33]
	GmIDT2	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	A-ring	[33]
	GmPT3	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	Unknown	[33]
	GmC4DT	Glycine max (L.) Merr.	DMAPP	Coumestrol	C-4	[33]
	GmG2DT	Glycine max (L.) Merr.	DMAPP	Glycinol	C-2	[33]
	GmPT01	Glycine max (L.) Merr.	DMAPP	Glycinol	C-2	[34]
	PcM4DT	Psoralea corylifolia Linn.	DMAPP	Maackiain, medicarpin	C-4	[35]
	PcPT11	Psoralea corylifolia Linn.	DMAPP	Genistein, apigenin, isorhamnetin, etc.	C-6	[36]
	MaIDT	Morus alba L.	DMAPP, GPP	Genistein, isoliquiritigenin, apigenin, etc.	C-3′	[37]
	CtIDT	Cudrania tricuspidata (Carr.) Bur.	DMAPP, GPP	Genistein, isoliquiritigenin, etc.	C-4′	[37]
	MaOGT	Morus alba L.	GPP, IPP, DMAPP, FPP, GGPP	Oxyresveratrol, resveratrol	C-4	[38]
	AhR4DT-1	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol, pinosylvin	C-4	[39]
	AhR3′DT-1	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-2	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-3	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-4	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	HcPT	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 7-trihydroxyxanthone, 1, 3, 5, 6-tetrahydroxyxanthone	C-8	[40]
	HcPT8px	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone	C-8	[41]
	HcPT8pat	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone	C-8	[41]
	HsPT8px	Hypericum sampsonii Hance	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 6, 7-tetrahydroxy-8-prenylxanthone	C-8	[41]
	HsPT8pat	Hypericum sampsonii Hance	DMAPP	1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone	C-8	[41]
	CsPT4	Cannabis sativa L.	DMAPP, GPP, FPP, GGPP	OA, etc.	C-3	[42]
	GlyMa_02G168000	Glycine max (L.) Merr.	DMAPP	OA	C-3	[43]
	MePT2	Murraya exotica L.	DMAPP	Quinolone	C-3	[25]
	ClaS	Clitocybe clavipes	GPP	Hydroquinone	C-2	[44]
	UbiA-297	Maribacter sp. MS6	FPP	8-Hydroxyquinoline-2-carboxylic acid, quinaldic acid, 1, 3-dihydroxynaphthalene, etc.	Unknown	[45]
	FtaB	Talaromyces variabilis H1	FPP	Indole-containing diketopiperazines	C-2	[46]
	Mpz10	Streptomyces sp.	DMAPP	1-Hydroxyphenazine, 1, 6-dihydroxyphenazine	C-4, C-9	[47]
	CnqPT1	Streptomyces sp. CNQ-509	GPP, DMAPP, FPP	1, 6-Dihydroxyphenazine, 1-hydroxyphenazine, flaviolin	1-OH, 2-OH	[48]
	CdnC	Penicillium funiculosum GWT2-24	FPP	Benzo-pyranone, benzo-cyclohexanone, etc.	C-5	[49]
	PgMpaA	Penicillium brevicompactum	FPP, GPP	5, 7-Dihydroxy-4-methylphthalde	C-6	[50]
ABBA type aPTs	Vib-PT	Stereum vibrans	DMAPP, GPP, FPP, GGPP	4-Hydroxybenzyl alcohol, 4-hydroxybenzaldehyde, etc.	3-OH, 4-OH, C-3	[51]
	AmbP3	Fischerella ambigua UTEX1903	DMAPP, GPP	cis-Indole nitrile, hapalindole U, hapalindole G, hapalindole A	C-2, C-3	[52, 53]
	FamD2	Fischerella ambigua UTEX1903	DMAPP, GPP	cis-Indole nitrile	C-2, C-3	[52]
	CnqP2	Streptomyces sp. CNQ-509	GPP, DMAPP	Genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene	7-OH, C-5, C-1	[54]
	CnqP3	Streptomyces sp. CNQ-509	GPP, DMAPP	Flaviolin, genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene	7-OH, C-5, C-1	[54]
	CnqP4	Streptomyces sp. CNQ-509	GPP	2, 7-Dihydroxynaphthalene	C-1	[54]
	CnqP5	Streptomyces sp. CNQ-509	DMAPP	1, 6-Dihydroxynaphthalene	C-5	[54]
	CnqP6	Streptomyces sp. CNQ-509	GPP	Genistein	7-OH	[54]
	ShFPT	Streptomyces sp. NT11	DMAPP	Naringenin	C-6	[55]
DMATS type aPTs	7-DMATS	Neosartorya sp.	DMAPP	L-Tryptophan, simple indole derivatives	C-7	[56]
	EchPT1	Aspergillus ruber CBS 135680	DMAPP	cyclo-L-Trp-L-Ala	C-2	[57]
	EchPT2	Aspergillus ruber CBS 135680	DMAPP	Preechinulin, etc.	Unknown	[57]
	SAML0654	Streptomyces ambofaciens	DMAPP, GPP	Tryptophan, tryptophan derivatives, naphthol, etc.	C-6	[58]
	Strvi8510	Streptomyces violaceusniger	DMAPP, GPP	Tryptophan, tryptophan derivatives, naphthol, etc.	C-6	[58]
	PriB	Streptomyces sp. RM-5-8	DMAPP, GPP, FPP, etc.	L-Tryptophan, simple indole derivatives, naphthol, anthraquinone, etc.	C-6	[59]
	CymD	Salinispora arenicola CNS-205	DMAPP	L-Tryptophan, indole, indole-like small molecules	N-1	[60]
	TleC	Streptomyces blastmyceticus NBRC 12747	GPP	Indolactam V	C-7	[61]
	TyrPT	Aspergillus niger	DMAPP	Tyrosine, tyrosine derivatives, tryptophan, tryptophan derivatives	4-OH, C-7	[62]
	DMATS1	Fusarium fujikuroi	DMAPP	L-Tryptophan	N-1	[63]
	RePT	Rasamsonia emersonii	DMAPP, GPP	L-Tryptophan, L-tyrosine, flavonoids, coumarins, etc.	C-7, N-1, etc.	[64]
	AcaPT	Taiwanofungus camphoratus	DMAPP	L-Tryptophan, flavonoids, coumarins, etc.	4'-OH, 7-OH, etc.	[65]
	AtaPT	Aspergillus terreus	DMAPP, GPP, FPP	Tryptophan derivatives, flavonoids, coumarins, etc.	C-3', C-4', C-6	[66]
Terpene cyclase-like aPTs	CqsB4	Streptomyces exfoliatus	DMAPP	Tricyclic carbazole	C-6	[67]
	NzsG	Streptomyces sp. MA37	DMAPP	Tricyclic carbazole	C-6	[68]
	LdqG	Streptomyces sp. LHW2432	CLPP	Tricyclic carbazole	C-6	[69]
	LvqB4	Streptomyces viridochromogenes 2942-SVS3	CLPP	Tricyclic carbazole	C-6	[70]
	AaTPS	Alternaria alternata TPF6	DMAPP	Indole, indole derivatives	N-1, C-3	[71]
	FgGS	Fusarium graminearum	DMAPP, GPP	Indole, indole derivatives	N-1, C-3	[71]

Type	Protein	Species	Prenyl donor	Substrate	Prenyl substitution site	Ref.
Membrane-bound UbiA type aPTs	AfUbiA	Archaeoglobus fulgidus	FPP, GPP, GGPP	PHB	C-3	[6]
	XimB	Streptomyces xiamenensis 318	FPP, GPP, GGPP	PHB	C-3	[7]
	SmPPT	Salvia miltiorrhiza Bunge	Polyprenyl-PP	PHB	C-3	[8]
	AePGT	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	AePGT4	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	AePGT6	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	MtMenA	Mycobacterium tuberculosis	FPP, polyprenyl-PP	DHNA	C-3	[10]
	BsMenA	Bacillus subtilis	FPP, GPP, GGPP, polyprenyl-PP	DHNA	C-3	[11]
	RcDT1	Rubia cordifolia L.	DMAPP	DHNA	C-3	[12]
	MmUBIAD1	Mus musculus	GGPP	Menadione	C-3	[13]
	CtHPT	Clitoria ternatea L.	PDP	HGA	C-3	[14]
	RTD1	Oryza sativa L.	PDP	HGA	C-3	[15]
	HlPT1L	Humulus lupulus L.	SDP	HGA	C-3	[16]
	HlPT2	Humulus lupulus L.	SDP	HGA	C-3	[16]
	PcPT	Petroselinum crispum (Mill.) Hill	DMAPP	Umbelliferone	C-6, C-8	[17]
	PsPT1	Pastinaca sativa L.	DMAPP	Umbelliferone	C-6	[18]
	PsPT2	Pastinaca sativa L.	DMAPP	Umbelliferone	C-8	[18]
	AsPT1	Angelica sinensis (Oliv.) Diels	DMAPP	Umbelliferone	C-6	[19]
	AsPT2	Angelica sinensis (Oliv.) Diels	DMAPP	Umbelliferone	C-8	[19]
	PpPT1	Peucedanum praeruptorum Dunn	DMAPP	Umbelliferone	C-6	[20]
	PpPT2	Peucedanum praeruptorum Dunn	DMAPP	Umbelliferone	C-8	[20]
	ClPT1	Citrus limon (L.) Burm. F.	GPP	Umbelliferone, esculetine, 5, 7-dihydroxycoumarin, 5-methoxy-7-hydroxycoumarin	C-8	[21]
	FcPT1a	Ficus carica Linn.	DMAPP	Umbelliferone, 5-methoxy-7-hydroxycoumarin	C-6	[22]
	FcPT1b	Ficus carica Linn.	DMAPP	Umbelliferone	C-6	[22]
	AcPT1	Artemisia capillaris Thunb.	DMAPP, GPP	p-Coumaric acid, ferulate, drupanin	C-3, C-5	[23]
	CpPT1	Citrus paradisi Macf.	GPP	5, 7-Dihydroxycoumarin, 5-hydroxy-7-methoxycoumarin, xanthotoxol, bergaptol, 8-hydroxybergapten	5-OH, 8-OH	[24]
	AkPT1	Angelica keiskei Koidz.	DMAPP	Bergaptol, xanthotoxol	C-5, C-8	[24]
	MePT1	Murraya exotica L.	GPP	Umbelliferone	C-6, C-8, 7-OH	[25]
	EsPT2	Epimedium sagittatum (Sieb. et Zucc.) Maxim.	DMAPP	Kaempferol, kaempferide, naringenin	C-8	[26]
	EpPT8	Epimedium pubescens Maxim.	DMAPP	Kaempferol, quercetin, apigenin	C-8	[27]
	LaPT2	Lupinus albus L.	DMAPP	Kaempferol, quercetin, fisetin, galangin, myricetin, naringenin	C-8	[28]
	AhPT1	Artocarpus heterophyllus Lam.	DMAPP	Genistein, 6-hydroxyflavone, etc.	C-6, C-5	[29]
	GuA6DT	Glycyrrhiza uralensis Fisch.	DMAPP, GPP	Apigenin, chrysin, luteolin, etc.	C-6	[30]
	GuILDT	Glycyrrhiza uralensis Fisch.	DMAPP	Naringenin chalcone, 2′, 4′-dihydroxychalcone, etc.	C-3′	[31]
	LjG6DT	Lotus corniculatus L.	DMAPP	Genistein	C-6	[32]
	GmIDT1	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	B-ring	[33]
	GmIDT2	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	A-ring	[33]
	GmPT3	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	Unknown	[33]
	GmC4DT	Glycine max (L.) Merr.	DMAPP	Coumestrol	C-4	[33]
	GmG2DT	Glycine max (L.) Merr.	DMAPP	Glycinol	C-2	[33]
	GmPT01	Glycine max (L.) Merr.	DMAPP	Glycinol	C-2	[34]
	PcM4DT	Psoralea corylifolia Linn.	DMAPP	Maackiain, medicarpin	C-4	[35]
	PcPT11	Psoralea corylifolia Linn.	DMAPP	Genistein, apigenin, isorhamnetin, etc.	C-6	[36]
	MaIDT	Morus alba L.	DMAPP, GPP	Genistein, isoliquiritigenin, apigenin, etc.	C-3′	[37]
	CtIDT	Cudrania tricuspidata (Carr.) Bur.	DMAPP, GPP	Genistein, isoliquiritigenin, etc.	C-4′	[37]
	MaOGT	Morus alba L.	GPP, IPP, DMAPP, FPP, GGPP	Oxyresveratrol, resveratrol	C-4	[38]
	AhR4DT-1	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol, pinosylvin	C-4	[39]
	AhR3′DT-1	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-2	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-3	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-4	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	HcPT	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 7-trihydroxyxanthone, 1, 3, 5, 6-tetrahydroxyxanthone	C-8	[40]
	HcPT8px	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone	C-8	[41]
	HcPT8pat	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone	C-8	[41]
	HsPT8px	Hypericum sampsonii Hance	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 6, 7-tetrahydroxy-8-prenylxanthone	C-8	[41]
	HsPT8pat	Hypericum sampsonii Hance	DMAPP	1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone	C-8	[41]
	CsPT4	Cannabis sativa L.	DMAPP, GPP, FPP, GGPP	OA, etc.	C-3	[42]
	GlyMa_02G168000	Glycine max (L.) Merr.	DMAPP	OA	C-3	[43]
	MePT2	Murraya exotica L.	DMAPP	Quinolone	C-3	[25]
	ClaS	Clitocybe clavipes	GPP	Hydroquinone	C-2	[44]
	UbiA-297	Maribacter sp. MS6	FPP	8-Hydroxyquinoline-2-carboxylic acid, quinaldic acid, 1, 3-dihydroxynaphthalene, etc.	Unknown	[45]
	FtaB	Talaromyces variabilis H1	FPP	Indole-containing diketopiperazines	C-2	[46]
	Mpz10	Streptomyces sp.	DMAPP	1-Hydroxyphenazine, 1, 6-dihydroxyphenazine	C-4, C-9	[47]
	CnqPT1	Streptomyces sp. CNQ-509	GPP, DMAPP, FPP	1, 6-Dihydroxyphenazine, 1-hydroxyphenazine, flaviolin	1-OH, 2-OH	[48]
	CdnC	Penicillium funiculosum GWT2-24	FPP	Benzo-pyranone, benzo-cyclohexanone, etc.	C-5	[49]
	PgMpaA	Penicillium brevicompactum	FPP, GPP	5, 7-Dihydroxy-4-methylphthalde	C-6	[50]
ABBA type aPTs	Vib-PT	Stereum vibrans	DMAPP, GPP, FPP, GGPP	4-Hydroxybenzyl alcohol, 4-hydroxybenzaldehyde, etc.	3-OH, 4-OH, C-3	[51]
	AmbP3	Fischerella ambigua UTEX1903	DMAPP, GPP	cis-Indole nitrile, hapalindole U, hapalindole G, hapalindole A	C-2, C-3	[52, 53]
	FamD2	Fischerella ambigua UTEX1903	DMAPP, GPP	cis-Indole nitrile	C-2, C-3	[52]
	CnqP2	Streptomyces sp. CNQ-509	GPP, DMAPP	Genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene	7-OH, C-5, C-1	[54]
	CnqP3	Streptomyces sp. CNQ-509	GPP, DMAPP	Flaviolin, genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene	7-OH, C-5, C-1	[54]
	CnqP4	Streptomyces sp. CNQ-509	GPP	2, 7-Dihydroxynaphthalene	C-1	[54]
	CnqP5	Streptomyces sp. CNQ-509	DMAPP	1, 6-Dihydroxynaphthalene	C-5	[54]
	CnqP6	Streptomyces sp. CNQ-509	GPP	Genistein	7-OH	[54]
	ShFPT	Streptomyces sp. NT11	DMAPP	Naringenin	C-6	[55]
DMATS type aPTs	7-DMATS	Neosartorya sp.	DMAPP	L-Tryptophan, simple indole derivatives	C-7	[56]
	EchPT1	Aspergillus ruber CBS 135680	DMAPP	cyclo-L-Trp-L-Ala	C-2	[57]
	EchPT2	Aspergillus ruber CBS 135680	DMAPP	Preechinulin, etc.	Unknown	[57]
	SAML0654	Streptomyces ambofaciens	DMAPP, GPP	Tryptophan, tryptophan derivatives, naphthol, etc.	C-6	[58]
	Strvi8510	Streptomyces violaceusniger	DMAPP, GPP	Tryptophan, tryptophan derivatives, naphthol, etc.	C-6	[58]
	PriB	Streptomyces sp. RM-5-8	DMAPP, GPP, FPP, etc.	L-Tryptophan, simple indole derivatives, naphthol, anthraquinone, etc.	C-6	[59]
	CymD	Salinispora arenicola CNS-205	DMAPP	L-Tryptophan, indole, indole-like small molecules	N-1	[60]
	TleC	Streptomyces blastmyceticus NBRC 12747	GPP	Indolactam V	C-7	[61]
	TyrPT	Aspergillus niger	DMAPP	Tyrosine, tyrosine derivatives, tryptophan, tryptophan derivatives	4-OH, C-7	[62]
	DMATS1	Fusarium fujikuroi	DMAPP	L-Tryptophan	N-1	[63]
	RePT	Rasamsonia emersonii	DMAPP, GPP	L-Tryptophan, L-tyrosine, flavonoids, coumarins, etc.	C-7, N-1, etc.	[64]
	AcaPT	Taiwanofungus camphoratus	DMAPP	L-Tryptophan, flavonoids, coumarins, etc.	4'-OH, 7-OH, etc.	[65]
	AtaPT	Aspergillus terreus	DMAPP, GPP, FPP	Tryptophan derivatives, flavonoids, coumarins, etc.	C-3', C-4', C-6	[66]
Terpene cyclase-like aPTs	CqsB4	Streptomyces exfoliatus	DMAPP	Tricyclic carbazole	C-6	[67]
	NzsG	Streptomyces sp. MA37	DMAPP	Tricyclic carbazole	C-6	[68]
	LdqG	Streptomyces sp. LHW2432	CLPP	Tricyclic carbazole	C-6	[69]
	LvqB4	Streptomyces viridochromogenes 2942-SVS3	CLPP	Tricyclic carbazole	C-6	[70]
	AaTPS	Alternaria alternata TPF6	DMAPP	Indole, indole derivatives	N-1, C-3	[71]
	FgGS	Fusarium graminearum	DMAPP, GPP	Indole, indole derivatives	N-1, C-3	[71]

修饰芳香族化合物的异戊烯基转移酶研究进展

PDF下载

谢萌 ¹ , 潘英妮 ¹ , 李宁 ¹^,^* , 訾佳辰 ²^,^*

药学学报 | 专题报道: 以多学科交叉探寻中药现代化发展之路 2025,60(3): 573-586

收起

药学学报 | 专题报道: 以多学科交叉探寻中药现代化发展之路 2025, 60(3): 573-586

修饰芳香族化合物的异戊烯基转移酶研究进展

全屏

谢萌¹, 潘英妮¹, 李宁¹^,^*, 訾佳辰²^,^*

作者信息

1.沈阳药科大学中药学院, 辽宁省重大慢病中药创新药重点实验室, 沈阳市中药药效物质研究与创新药开发重点实验室, 辽宁沈阳 110016

2.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 国家卫生健康委员会天然药物生物合成重点实验室, 中国医学科学院酶与天然药物生物催化重点实验室, 北京 100050

通讯作者:

^*李宁, Tel: 86-24-43520739, E-mail: liningsypharm@163.com

訾佳辰, Tel: 86-10-50927375, E-mail: zijiachen@imm.ac.cn

Advances in prenyltransferases research for modifying aromatic natural products

Meng XIE¹, Ying-ni PAN¹, Ning LI¹^,^*, Jia-chen ZI²^,^*

Affiliations

1. Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning Province, Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang City, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biosynthesis of Natural Products, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

出版时间: 2025-03-12 doi: 10.16438/j.0513-4870.2024-1067

文章导航

摘要

收起

具有异戊烯基取代的芳香族天然产物(prenylated aromatic natural products, PANPs) 广泛存在于自然界中。由于核心骨架的变化(香豆素、木脂素、苯甲酸/苯甲醇、黄酮、氧杂蒽酮、蒽醌和芳香生物碱等) 以及异戊烯基的类型、取代位置和是否环合的差别, PANPs展现出丰富的结构多样性。多样的结构也赋予了PANPs多样的活性, 例如抗菌、抗氧化、抗肿瘤和消炎镇痛等作用。因此, PANPs具有很好的药物开发价值。对于当归、前胡及补骨脂等中药材, PANPs是其重要的药效物质。值得注意的是, 异戊烯基往往是关键药效团。根据亲缘关系以及结构特征, PANPs生物合成途径中的芳香族异戊烯基转移酶(aromatic prenyltransferases, aPTs) 可分为膜结合(membrane-bound) aPTs (UbiA型)、具有PT桶状(PT barrel) 结构的可溶性aPTs (ABBA型和DMATS型) 以及类似萜合酶的aPTs。本文综述了近10年发现的94个不同类型的aPTs, 重点总结了它们的底物选择性、区域选择性、进化关系及结构特征, 为新颖aPTs的发现、改造, 以及活性PANPs的结构修饰和生物制造提供思路。

关键词

异戊烯基芳香族化合物 / 芳香族异戊烯基转移酶 / 底物选择性 / 区域选择性 / 生物合成

Abstract

收起

Prenylated aromatic natural products (PANPs) are widely distributed in nature. PANPs exhibit a great structural diversity due to their various core scaffolds (coumarin, lignan, benzoic acid/benzyl alcohol, flavonoid, xanthone, anthraquinone, and aromatic alkaloid, etc.) and the distinct types and substitution sites of isoprenoid moieties which may possess either linear or cyclic structures. The structural diversity of PANPs endow them with various bioactivities including anti-bacterial, anti-oxidation, anti-cancer, anti-inflammatory and analgesic effects, which makes them a group of highly promising molecules for drug development. Notably, isoprenoid moieties are often the indispensable pharmacophores in these active PANPs. Aromatic prenyltransferases (aPTs) are responsible for prenylation in the biosynthesis of PANPs. aPTs can be divided into three classes according to their evolutionary relationships and structural features, i.e. membrane-bound aPTs (UbiA type), soluble aPTs with a PT barrel structure (ABBA type and DMATS type) and terpene synthase-like aPTs. Herein, we summarize 94 aPTs belonging to the different classes which were characterized in the past ten years, in particular introduce their substrate selectivity/tolerance, regioselectivity, evolutionary relationships and structural features. This would provide cues for discovery and engineering of new aPTs, and modification and bio-production of active PANPs.

Key words

prenylated aromatic natural product / aromatic prenyltransferase / substrate selectivity / regioselectivity / biosynthesis

引用本文

谢萌, 潘英妮, 李宁, 訾佳辰. 修饰芳香族化合物的异戊烯基转移酶研究进展. 药学学报, 2025 , 60 (3) : 573 -586 . DOI: 10.16438/j.0513-4870.2024-1067

Meng XIE, Ying-ni PAN, Ning LI, Jia-chen ZI. Advances in prenyltransferases research for modifying aromatic natural products[J]. Acta Pharmaceutica Sinica, 2025 , 60 (3) : 573 -586 . DOI: 10.16438/j.0513-4870.2024-1067

正文

收起

含有异戊烯基取代的芳香族天然产物(prenylated aromatic natural products, PANPs) 广泛存在于微生物、植物和动物中, 具有抗氧化、抗炎、抗肿瘤、抗菌、抗疟及神经保护等药理活性^[1]。PANPs的核心骨架类型主要包括: 香豆素、木脂素、苯甲酸/苯甲醇、黄酮、氧杂蒽酮、蒽醌和芳香生物碱等; 其异戊烯基取代单元主要包括: 二甲基烯丙基(C₅)、香叶基(C₁₀)、法尼烯基(C₁₅) 和香叶基香叶基(C₂₀)。在不同位置取代不同链长的异戊烯基单元, 很大程度上丰富了结构的多样性, 同时这些异戊烯基单元对PANPs的药效活性也至关重要^[2]。

在PANPs的生物合成中, 芳香族异戊烯基转移酶(aromatic prenyltransferases, aPTs) 负责识别异戊烯基供体, 将以上各种异戊烯基单元转移至芳香类核心骨架受体上, 所形成的共价键有碳-碳键、碳-氧键和碳-氮键等。主要异戊烯基供体包括: 二甲基丙烯焦磷酸(dimethylallyl pyrophosphate, DMAPP)、香叶基焦磷酸(geranyl diphosphate, GPP)、法尼烯基焦磷酸(farnesyl diphosphate, FPP) 及香叶基香叶基焦磷酸(geranylgeranyl pyrophosphate, GGPP) 等。从机制上讲, aPTs催化的异戊烯基转移反应可分为3个步骤: 异戊烯基供体脱焦磷酸、异戊烯基碳正离子亲和进攻受体从而生成中间体σ复合物, 以及σ复合物脱质子得到终产物^[3]。目前从微生物、动物和植物中均发现了aPTs。根据亲缘关系以及结构特征, aPTs可被分为3类: 膜结合(membrane-bound) aPTs (UbiA型)、具有PT桶状(PT barrel) 结构的可溶性aPTs (ABBA型和DMATS型), 以及类似萜合酶的aPTs^[3-5]。进化树分析结果显示: 可溶性aPTs和类似萜合酶的aPTs具有较近的亲缘关系, 而膜结合的UbiA型aPTs明显处于进化树的另一分支(图 1)。本文总结了94个近10年发现的aPTs (图 1和表 1^[6-71]), 下面分类展开介绍。

1 UbiA型膜结合(membrane-bound) aPTs

收起

2014年, 第一个UbiA型aPT (Aeropyrum pernix中的ApUbiA) 的结构被解析^[4]。ApUbiA由9个跨膜螺旋围成中心空腔; 并且3个位于膜外的螺旋/无规则回路结构单元(helix/loop regions) HL2-3、HL4-5和HL6-7组成一个“帽结构域” (cap domain), 覆盖于空腔口; 空腔从侧面朝向磷脂双分子层开口, 即具有一个lateral portal (图 2)。3个保守基序DxxxD、DxxGD和YxxxK分别位于HL2-3、HL6-7和HL4-5, 在镁离子和水分子参与下, 负责结合底物并催化反应。因此, UbiA型aPTs依赖于Mg²⁺、Mn²⁺、Co²⁺和Ca²⁺等二价金属离子。在异戊烯基供体脱焦磷酸生成碳正离子阶段, 两个保守天冬氨酸基序直接或间接通过镁离子与焦磷酸基团结合, 诱导碳正离子形成; 然后, 异戊烯基碳正离子进攻芳香化合物受体, 形成带正电荷的σ复合物; 最后, 由焦磷酸(被天冬氨酸基序结合) 从σ复合物夺取质子后, 得到终产物^[4]。

目前从微生物、植物和动物中都发现了UbiA型aPTs, 而以上结构特征以及活性中心的氨基酸基序在不同物种来源的UbiA型aPTs中高度保守^{[3, 4]}。研究表明催化相同类型底物异戊烯基化的UbiA型aPTs往往具有更近的亲缘关系(图 1)。

1.1 以对羟基苯甲酸(p-hydroxybenzoic acid, PHB) 为底物的UbiA型aPTs

该类UbiA型aPTs主要催化PHB C-3位的异戊烯基化, 所得产物是泛醌(ubiquinone) 的生物合成前体。泛醌是细菌和线粒体呼吸链所必需的电子载体; 其还原形式(即泛醇, ubiquinol) 具有强抗氧化活性, 能修复脂质过氧化, 从而保护膜脂质^[72]。因此, 该类aPTs广泛存在于微生物和动植物中。微生物来源的该类酶包括: Archaeoglobus fulgidus中的AfUbiA^[6]和Streptomyces xiamenensis 318中的XimB^[7]。二者均能接受GPP、FPP和GGPP为异戊烯基供体底物。植物来源的该类酶包括: 丹参(Salvia miltiorrhiza Bunge) 中的SmPPT^[8]和软紫草[Arnebia euchroma (Royle) Johnst.] 中的AePGT、AePGT4和AePGT6^[9]。SmPPT以聚异戊烯基焦磷酸为供体, 分别生成ubiquinone Q9和ubiquinone Q10两种泛醌^[8]。AePGT、AePGT4和AePGT6以GPP为供体, 生成紫草素(shikonin) 的前体物质3-香叶基-4-羟基苯甲酸^[9]。动物中的对羟基苯甲酸aPTs为: 辅酶Q2, 聚异戊烯基转移酶(coenzyme Q2, polyprenyltransferase)。例如来自人类(Homo sapiens) 的HsCOQ2^[73]和来自小鼠(Mus musculus) 的MmCOQ2^[74], 但近10年中未发现新的动物源对羟基苯甲酸aPTs。

1.2 以1, 4-二羟基-2-萘甲酸(1, 4-dihydroxy-2-naphthoic acid, DHNA) 及2-甲基-1, 4-萘醌(menadione) 为底物的UbiA型aPTs

维生素K是一大类以2-甲基-1, 4-萘醌为核心骨架的化合物, 包括甲基萘醌(menaquinone) 和叶绿醌(phylloquinone) 等^[75]。维生素K在多种生化过程中扮演着重要角色, 例如酶的辅因子及电子载体等^[76]。微生物中的维生素K为甲基萘醌类化合物。在甲基萘醌生物合成途径中, 异戊烯基转移酶MenA以不同链长的异戊烯基焦磷酸为供体, 催化1, 4-二羟基-2-萘甲酸(DHNA) C-3位的异戊烯基化, 得到去甲基萘醌(demethylmenaquinone), 然后在甲基转移酶的催化下生成甲基萘醌。近10年, 从微生物中发现的MenA酶包括结核分枝杆菌(Mycobacterium tuberculosis) 中的MtMenA^[10]和枯草芽孢杆菌(Bacillus subtilis) 中的BsMenA^[11], 前者以FPP及聚异戊烯基焦磷酸为供体, 后者以GPP、FPP、GGPP及聚异戊烯基焦磷酸为供体。

从植物中发现的该类UbiA型aPTs主要以叶绿醇焦磷酸(phytyl diphosphate, PDP) 为供体, 催化DHNA的C-3位异戊烯基化, 因此被称为DHNA叶绿醇转移酶(1, 4-dihydroxy-2-napthoic acid phytyltransferase)。所得产物为叶绿醌的生物合成前体。而茜草(Rubia cordifolia L.) 中的RcDT1并不参与叶绿醌(初级代谢产物) 的合成, 而是参与次级代谢产物的生物合成。该酶以DMAPP为供体, 分别生成2-羧基-3-烯丙基-1, 4-萘醌和3-烯丙基-1, 4-萘醌, 二者均为茜草素型蒽醌的生物合成前体^[12]。

动物中的UBIAD1 (UbiA prenyltransferase containing 1) 与微生物中MenA具有显著的亲缘关系(图 1)。二者的区别在于MenA以DHNA为异戊烯基的受体, 而UBIAD1以2-甲基-1, 4-萘醌为异戊烯基的受体。因此, UBIAD1参与的甲基萘醌生物合成不需要甲基转移酶。近期的研究发现不同亚细胞定位的UBIAD1具有不同的催化功能。定位于线粒体膜上的UBIAD1参与甲基萘醌的生物合成^[75]; 而高尔基体中表达的UBIAD1参与泛醌COQ10的生成^[77]。近10年发现的该类酶有小鼠中的MmUBIAD1^[13]。

1.3 血红素O合成酶(heme O synthase, HOS)

血红素具有运输O₂以及感应NO和CO等功能, 在有氧呼吸中发挥重要作用^[78], 因此, 微生物、动物和植物中都存在血红素生物合成途径^[72]。HOS以FPP为供体底物, 将法尼烯基转移到血红素B (heme B) 的2-乙烯基上, 得到血红素O (heme O), 例如B. Subtilis中的CtaB^[79]。近10年, 未发现新HOS酶。

1.4 叶绿素合成酶(chlorophyll synthases, ChlG)

ChlG以PDP为供体底物, 在脱植基叶绿素(chlorophyllide) 的17-丙酸上引入植基, 生成叶绿素a (chlorophyll a)。ChlG也可以将香叶基香叶基转移至脱植基叶绿素上, 先生成香叶基香叶基叶绿素, 再通过一步还原反应生成叶绿素^[80]。例如水稻中的OsATG4^[81]。近10年, 未发现新ChlG酶。

1.5 尿黑酸异戊烯转移酶(homogentisate prenyltransferase, HGPT)

HGPT以尿黑酸(homogentisate acid, HGA) 为受体底物, 根据接受的供体底物不同分为3种类型: 尿黑酸植基转移酶(homogentisate phytyltransferase, HPT)、尿黑酸香叶基香叶基转移酶(homogentisate geranylgeranyl transferase, HGGT) 和尿黑酸茄尼基转移酶(homogentisate solanesyltransferase, HST)。HPT、HGGT和HST分别接受PDP、GGPP和茄烷基焦磷酸(solanesyl diphosphate, SDP) 为供体, 在HGA的C-3位引入异戊烯基, 所得产物分别为生育酚(tocopherol)、生育三烯酚(tocotrienol) 和质体醌(plastoquinone) 的生物合成前体。近10年发现的该类酶包括: 蝶豆(Clitoria ternatea L.) 中的CtHPT^[14]、水稻中的RTD1^[15]和啤酒花(Humulus lupulus L.) 中的HlPT1L和HlPT2^[16]。其中, CtHPT和RTD1为HPT, HlPT1L和HlPT2为HST。

1.6 以香豆素类化合物(coumarins) 为底物的UbiA型aPTs

从伞形科植物中发现了7个与补骨脂素和异补骨脂素生物合成相关的UbiA型aPTs, 包括: 欧芹[Petroselinum crispum (Mill.) Hill] 中的PcPT^[17]、欧防风(Pastinaca sativa L.) 中的PsPT1和PsPT2^[18]、当归[Angelica sinensis (Oliv.) Diels] 中的AsPT1和AsPT2^[19]以及前胡(Peucedanum praeruptorum Dunn) 中的PpPT1和PpPT2^[20]。这些aPTs都具有显著的底物专一性, 仅以DMAPP为异戊烯基供体, 仅接受伞形酮(umbelliferone) 为受体。PcPT主要生成C-6位异戊烯基化的产物以及少量C-8位异戊烯基化的产物, PsPT1、AsPT1和PpPT1催化伞形酮C-6位的异戊烯基化, 而PsPT2、AsPT2和PpPT2催化伞形酮C-8位的异戊烯基化。

从柠檬[Citrus limon (L.) Burm. F.] 中鉴定的ClPT1特异性地以GPP为异戊烯基供体, 分别催化伞形酮、七叶亭(esculetine)、5, 7-二羟基香豆素(5, 7-dihydroxycoumarin) 和7-羟基-5-甲氧基香豆素(5-methoxy-7-hydroxycoumarin) C-8位的异戊烯基化^[21]。无花果(Ficus carica Linn.) 中的FcPT1a和FcPT1b均特异性地以DMAPP为异戊烯基供体, 前者可催化伞形酮和7-羟基-5-甲氧基香豆素C-6位的异戊烯基化, 分别生成补骨脂素和佛手柑内酯的生物合成前体, 后者仅能催化伞形酮C-6位的异戊烯基化反应^[22]。茵陈蒿(Artemisia capillaris Thunb.) 中的AcPT1主要以DMAPP为异戊烯基供体, 可分别在苯丙素类化合物对香豆酸(p-coumaric acid) 和阿魏酸(ferulate) 的C-3位及drupanin的C-5位引入异戊烯基^[23]。

大多数植物源的UbiA型aPTs包括以上7个aPTs, 都催化C-C键连接的异戊烯基化反应, 但是也从植物中发现少数aPTs可在氧原子上引入异戊烯基。第一个发现的植物UbiA型O-aPT是芸香科葡萄柚(Citrus paradisi Macf.) 中的CpPT1。该酶特异性地以GPP为异戊烯基供体, 可在5, 7-二羟基香豆素、5-羟基-7-甲氧基香豆素(5-hydroxy-7-methoxycoumarin)、花椒毒酚(xanthotoxol)、香柑醇(bergaptol) 和8-羟基佛手苷内酯(8-hydroxybergapten) 的5-OH或8-OH上引入异戊烯基^[24]。明日叶(Angelica keiskei Koidz.) 中的AkPT1主要以DMAPP为供体, 催化香柑醇C-5位和花椒毒酚C-8位羟基的异戊烯基化^[24]。九里香(Murraya exotica L.) 的MePT1是唯一一个可以同时催化C-异戊烯基化和O-异戊烯基化的aPT; 该酶以GPP为供体, 在伞形酮C-6位、C-8位和7-OH位均可引入异戊烯基, 生成3种不同的异戊烯基化产物^[25]。

1.7 以黄酮类化合物(flavonoids) 为底物的UbiA型aPTs

大多数以黄酮类化合物为底物的UbiA型aPTs特异性地以DMAPP为异戊烯基供体, 可催化多种黄酮底物的异戊烯基化。这些酶包括: 箭叶淫羊藿[Epimedium sagittatum (Sieb. et Zucc.) Maxim.] 中的EsPT2^[26]、柔毛淫羊藿(Epimedium pubescens Maxim.) 中的EpPT8^[27]、白羽扇豆(Lupinus albus L.) 中鉴定的LaPT2^[28]、波罗蜜(Artocarpus heterophyllus Lam.) 中的AhPT1^[29]、甘草(Glycyrrhiza uralensis Fisch.) 中鉴定的GuA6DT^[30]和GuILDT^[31]、百脉根(Lotus corniculatus L.) 中鉴定的LjG6DT^[32]、大豆[Glycine max (L.) Merr.] 中的GmIDT1、GmIDT2、GmPT3、GmC4DT、GmG2DT^[33]和GmPT01^[34]以及补骨脂(Psoralea corylifolia Linn.) 中鉴定的PcM4DT^[35]和PcPT11^[36]。EsPT2可异戊烯基化山柰酚(kaempferol)、山柰素(kaempferide) 和柚皮素(naringenin) C-8位, 对山柰酚的选择性更高^[26]。EpPT8可异戊烯基化山柰酚、槲皮素(quercetin) 和芹菜素(apigenin) 的C-8位^[27]。LaPT2可异戊烯基化山柰酚、槲皮素、漆黄素(fisetin)、高良姜素(galangin)、杨梅素(myricetin) 和柚皮素的C-8位, 对山柰酚和槲皮素具有较高的选择性^[28]。AhPT1在Mg²⁺存在下催化染料木素(genistein) 等黄酮类化合物C-6位的异戊烯基化; 在Mn²⁺存在下, 催化6-羟基黄酮(6-hydroxyflavone) 及其衍生物C-5位的异戊烯基化^[29]。GuA6DT催化具有5, 7-二羟基取代黄酮C-6位的异戊烯基化^[30]。GuILDT催化柚皮素查尔酮(naringenin chalcone) 和2′, 4′-二羟基查尔酮(2′, 4′-dihydroxychalcone) 等具有4′-羟基查尔酮C-3′位的异戊烯基化^[31]。LjG6DT催化染料木素C-6位的异戊烯基化^[32]。GmIDT1、GmIDT2和GmPT3均可以大豆黄素(daidzein) 和染料木素为受体底物, GmIDT1在B-ring引入异戊烯基, GmIDT2在A-ring引入异戊烯基, GmPT3的产物尚未确定^[33]。GmC4DT在coumestrol的C-4位引入异戊烯基^[33]。GmG2DT和GmPT01在glycinol的C-2位引入异戊烯基^{[33, 34]}。PcM4DT催化高丽槐素(maackiain) 和美迪紫檀素(medicarpin) C-4位的异戊烯基化^[35]。PcPT11是目前发现的受体底物泛杂性最高的植物aPT, 可识别23种受体底物(22种黄酮类化合物和1种香豆素), 对受体的C-6位有较高的区域选择性^[36]。除以上特异性地以DMAPP为异戊烯基供体的aPTs外, 桑(Morus alba L.) 中的MaIDT和柘树[Cudrania tricuspidata (Carr.) Bur.] 中的CtIDT可以接受DMAPP和GPP为供体底物, 催化异甘草素(isoliquiritigenin) 等查尔酮和异黄酮的C-3′位的异戊烯基化; 此外, MaIDT还可以识别芹菜素, 而CtIDT不能识别^[37]。

1.8 以芪类化合物(stilbenoids) 为底物的UbiA型aPTs

桑中的MaOGT可接受IPP (isopentenyl pyrophosphate, IPP)、DMAPP、GPP、FPP和GGPP多种异戊烯基供体, 在氧化白藜芦醇(oxyresveratrol) 和白藜芦醇(resveratrol) 的C-4位上引入异戊烯基, 其对GPP的选择性最高^[38]。落花生(Arachis hypogaea L.) 中的AhR4DT-1和AhR3′DT-1特异性地以DMAPP为异戊烯基供体, 分别催化白皮杉醇(piceatannol) 和氧化白藜芦醇C-4和C-3′位的异戊烯基化; 此外, AhR4DT-1还可以催化赤松素(pinosylvin) C-4位的异戊烯基化^[39]。

1.9 以氧杂蒽酮(xanthones) 为底物的UbiA型aPTs

冬绿金丝桃(Hypericum calycinum L.) 中的HcPT^[40]、HcPT8px和HcPT8pat^[41]以及元宝草(Hypericum sampsonii Hance) 中鉴定的HsPT8px和HsPT8pat^[41]均以DMAPP为供体, 以各种氧杂蒽酮为底物。HcPT主要催化1, 3, 6, 7-四羟基氧杂蒽酮(1, 3, 6, 7-tetrahydroxyxanthone) 和1, 3, 7-三羟基氧杂蒽酮(1, 3, 7-trihydroxyxanthone) C-8位的异戊烯基化; 以1, 3, 5, 6-四羟基氧杂蒽酮(1, 3, 5, 6-tetrahydroxyxanthone) 为底物时, 效率极低^[40]。HcPT8px催化1, 3, 6, 7-四羟基氧杂蒽酮C-8位的异戊烯基化。HsPT8px催化1, 3, 6, 7-四羟基氧杂蒽酮和1, 3, 6, 7-四羟基-8-异戊二烯基氧杂蒽酮(1, 3, 6, 7-tetrahydroxy-8-prenylxanthone) C-8位的异戊烯基化。HcPT8pat和HsPT8pat催化1, 3, 6, 7-四羟基-8-异戊二烯基氧杂蒽酮C-8位的异戊烯基化, 生成patulone; 还可以催化两个二甲基烯丙基同时转移至1, 3, 6, 7-四羟基氧杂蒽酮C-8位上, 直接生成patulone^[41]。

1.10 以橄榄酸(olivetolic acid, OA) 为底物的UbiA型aPTs

大麻(Cannabis sativa L.) 中的CsPT4^[42]和大豆中的GlyMa_02G168000^[43]以DMAPP为异戊烯基供体, 催化橄榄酸C-3位的异戊烯基化, 生成大麻酚类化合物的生物合成前体大麻萜酚酸(cannabigerolic acid)。其中CsPT4还可接受GPP、FPP和GGPP为异戊烯基供体, 异戊烯基化C-6位存在不同长度烷基取代和苯乙基取代的橄榄酸^[42]。

1.11 以其他芳香类化合物为底物的UbiA型aPTs

九里香中的MePT2是第一个被发现可以异戊烯基化喹诺酮类生物碱的植物aPT, 以DMAPP为异戊烯基供体, 在多种喹诺酮类生物碱的C-3位上引入异戊烯基, 其产物为白鲜碱(dictamnine)、弗林辛(flindersin) 和茵芋碱(skimmiamine) 的生物合成前体^[25]。棒柄杯伞(Clitocybe clavipes) 中的ClaS特异性地以GPP为供体, 在对苯二酚(hydroquinone) 及其单取代衍生物的C-2位引入异戊烯基; ClaS的突变体H73R的受体底物变为对羟基苯甲酸及其衍生物^[44]。

此外, 从微生物中也发现了一些UbiA型aPTs。海杆菌属Maribacter sp. MS6中的UbiA-297对2-羧基-8-羟基喹啉(8-hydroxyquinoline-2-carboxylic acid) 和2-羧基喹啉(quinaldic acid) 的催化效率最高, 在其芳香环上引入法尼烯基。另外, 它还可以接受8-羟基喹啉(8-hydroxyquinoline)、1, 3-二羟基萘(1, 3-dihydroxynaphthalene)、4-甲基伞形酮(4-methylumbelliferone) 和黄尿酸(xanthurenic acid)^[45]。篮状菌属Talaromyces variabilis H1中的FtaB是第一个可以催化二酮哌嗪异戊烯基化的UbiA型aPT, 该酶以FPP为异戊烯基供体, 将异戊烯基引入含吲哚的二酮哌嗪(indole-containing diketopiperazines) 及其类似物的C-2位上^[46]。S. sp.中的Mpz10是首个可以催化吩嗪类化合物异戊烯基化的UbiA型aPT, 该酶特异性地以DMAPP为异戊烯基供体, 在1-羟基吩嗪(1-hydroxyphenazine) 和1, 6-二羟基吩嗪(1, 6-dihydroxyphenazine) 的C-4或C-9位上引入异戊烯基^[47]。S. sp. CNQ-509中的CnqPT1是一种O-aPT, 主要以DMAPP、GPP和FPP为供体, 在1, 6-二羟基吩嗪、1-羟基吩嗪的C-1位羟基和flaviolin的C-2位羟基上引入异戊烯基, 其对GPP的选择性最高^[48]。绳状青霉(Penicillium funiculosum GWT2-24) 中的CdnC以FPP为供体, 催化苯骈吡喃酮(benzo-pyranone) 和苯骈环己酮(benzo-cyclohexanone) C-5位的异戊烯基化, 它还可以接受2, 4-二羟基苯甲醛(2, 4-dihydroxybenzaldehyde)、3, 5-二羟基-4-甲基苯甲醛(3, 5-dihydroxy-4-methylbenzaldehyde)、4-羟基苯甲醛(4-hydroxybenzaldehyde) 和3, 5-二羟基苯甲酸(3, 5-dihydroxybenzoic acid) 为底物^[49]。短密青霉(P. brevicompactum) 中的PgMpaA以GPP和FPP为异戊烯基供体, 催化5, 7-二羟基-4-甲基苯酞(5, 7-dihydroxy-4-methylphthalde) C-6位的异戊烯基化, 其对GPP选择性更高^[50]。

2 具有PT桶状(PT barrel) 结构的可溶性aPTs

收起

依据进化的亲缘关系, 具有PT桶状(PT barrel) 结构的可溶性aPTs可分为两个亚家族, 分别为以二甲基烯丙基色氨酸合酶(dimethylallyl tryptophan synthase, DMATS) 为代表的亚家族(即DMATS型aPTs) 以及以苯酚/吩嗪异戊烯基转移酶(如CloQ和NphB) 为代表的亚家族(phenol/phenazine PTs, 即ABBA型aPTs)^[5]。这两种aPTs具有共同的结构特征, 即由5个重复的ααββ二级结构单元围成的桶状结构(被称为PT桶状结构); 其中, 反平行排列的β-折叠股(β-strands) 位于内部, α-螺旋位于外部而暴露于溶液中^{[82, 83]}。不同于UbiA型aPTs, 二者都不具有(N/D) DxxD基序。其中, DMATS型aPTs均不依赖于二价金属离子, 如FgaPT2^[82](图 3A)。在脱焦磷酸阶段, DMATS型aPTs中的一系列带正电荷的残基(如精氨酸和赖氨酸) 可稳定焦磷酸根, 此外多个酪氨酸(tyrosine shield) 可与焦磷酸根的氧原子形成氢键, 从而进一步降低脱焦磷酸反应的能垒并稳定焦磷酸根; 最后, 赖氨酸(如FgaPT2中的K174) 负责夺取σ复合物的质子, 从而生成终产物^[82]。ABBA型aPTs可进一步分为两种类型: 一种为二价金属(镁离子等) 依赖型aPTs (如NphB^{[82, 84]}, 图 3B); 另一种为非二价金属(镁离子等) 依赖型aPTs (如MpnD^[85]), 采用带正电荷的残基结合焦磷酸(图 3C)^[83]。对于金属依赖型的ABBA型aPTs, 采用单个天冬氨酸残基(如NphB中的Asp62) 与二价金属离子配位, 促进异戊烯基供体脱焦磷酸^[84]。非金属依赖的ABBA型aPTs的脱焦磷酸反应与DMATS型aPTs类似, 也通过一系列带正电荷的残基和tyrosine shield促进异戊烯基供体脱焦磷酸并稳定异戊烯基碳正离子^[85]; 最后, 通过侧链具有接受质子的氮原子的氨基酸(如: 赖氨酸和组氨酸) 或以水分子介导的方式夺取σ复合物的质子, 从而生成终产物^[82]。

目前所发现的具有PT桶状结构的可溶性aPTs均源于微生物。与UbiA型aPTs相似, 这类可溶性aPTs也表现出受体底物选择性与其亲缘关系的关联性^[5]。因此, 本部分也根据受体底物的结构类型, 进行分类介绍。

2.1 ABBA型aPTs

ABBA型aPTs主要催化二羟基萘类、黄酮类、4-羟苯基丙酮酸和聚酮类等化合物的异戊烯基化^[3]。韧革菌属Stereum vibrans中的Vib-PT以DMAPP、GPP、FPP和GGPP为供体, 催化4-羟基苯甲醇(4-hydroxybenzyl alcohol) C-3和4-OH位以及4-羟基苯甲醛C-3位的异戊烯基化反应, 另外Vib-PT还可以接受3, 4-二羟基苯甲醛(3, 4-dihydroxybenzaldehyde)、4-羟基苯甲酸(4-hydroxybenzoic acid)、L-酪氨酸(L-tyrosine) 和L-色氨酸(L-tryptophan)^[51]。从可疑飞氏藻(Fischerella ambigua UTEX1903) 中的AmbP3和FamD2可在cis-indole nitrile C-2位和C-3位同时引入二甲基烯丙基或香叶基, 分别生成dimethylallylated cis-indole nitrile和geranylated cis-indole nitrile, 后者是hapalindoles型生物碱的前体化合物^[52]。此外, AmbP3还可以催化hapalindole U和hapalindole G C-2位的反向异戊烯基化, 分别生成ambiguine型吲哚类生物碱的前体化合物ambiguine H和ambiguine A; 还可以催化hapalindole A C-2位的正向异戊烯基化反应^[53]。从S. sp. CNQ-509中鉴定出多个aPTs, 这些酶主要以GPP和DMAPP为供体, 可以在多种具有萘环结构的化合物的不同位置引入异戊烯基(如表 1所示)^[54]。S. sp. NT11中的ShFPT以DMAPP为供体, 特异性地催化柚皮素的C-6位异戊烯基化^[55]。

2.2 DMATS型aPTs

DMATS型aPTs主要催化L-色氨酸、吲哚衍生物和含色氨酸的环二肽的异戊烯基化^[3]。新萨托菌属Neosartorya sp.中的7-DMATS以DMAPP为供体, 催化L-色氨酸和某些简单吲哚衍生物(simple indole derivatives) C-7位的异戊烯基化^[56]。从赤曲霉(Aspergillus ruber CBS 135680) 中鉴定出EchPT1和EchPT2二者均以DMAPP为供体。前者催化cyclo-L-Trp-L-Ala C-2位的反向异戊烯基化, 生成preechinulin; 后者可将二甲基烯丙基转移至preechinulin苯环的不同位点, 生成具有多个异戊烯基取代的产物^[57]。S. ambofaciens和S. violaceusniger中的SAML0654和Strvi8510都能以DMAPP和GPP为异戊烯基供体, 催化色氨酸及其衍生物(tryptophan derivatives) C-6位的异戊烯基化, 另外它们还可以催化一些萘酚(naphthol) 的异戊烯基化^[58]。S. sp. RM-5-8的PriB能以DMAPP、GPP、FPP及其类似物为供体, 异戊烯基化L-色氨酸的C-6位; 此外, 还可以接受简单吲哚衍生物、萘酚和蒽醌(anthraquinone) 等化合物作为底物^[59]。盐孢菌属Salinispora arenicola CNS-205中的CymD以DMAPP为异戊烯基供体, 催化L-色氨酸N-1位的反向异戊烯基化, 该酶对其他吲哚(indole) 和类吲哚小分子(indole-like small molecules) 也有催化活性^[60]。S. blastmyceticus NBRC 12747中的TleC以GPP为供体, 在吲哚内酰胺V (indolactam V) 的C-7位引入异戊烯基, 生成吲哚生物碱teleocidin B的生物合成前体iyngbyatoxin A^[61]。黑曲霉菌(A. niger) 中的TyrPT以DMAPP为供体, 催化酪氨酸及其衍生物4-OH的O-异戊烯基化以及色氨酸及其衍生物C-7位的C-异戊烯基化^[62]。藤仓镰刀菌(Fusarium fujikuroi) 中的DMATS1以DMAPP为供体, 催化L-色氨酸N-1位的反向异戊烯基化^[63]。一些真菌来源的aPTs表现出较高的异戊烯基受体底物泛杂性。Rasamsonia emersonii中的RePT以DMAPP为供体, 可催化L-色氨酸、L-酪氨酸、芪类、类黄酮和香豆素等类型化合物的异戊烯基化。该酶的功能主要表现为O-aPT; 而以L-色氨酸为底物时, 它优先催化C-7位的异戊烯基化, 但也可生成少量N-1位的反向异戊烯基化产物^[64]。真菌牛樟芝(Taiwanofungus camphoratus) 中的AcaPT以DMAPP为异戊烯基供体, 催化L-色氨酸、类黄酮、香豆素和芪类等多种芳香族化合物的异戊烯基化^[65]。土曲霉(A. terreus) 中的AtaPT具有更广泛的底物泛杂性, 能以DMAPP、GPP和FPP为异戊烯基供体, 催化72种芳香族化合物的异戊烯基化, 例如: 色氨酸衍生物、木脂素类、类黄酮、香豆素和氧杂蒽酮等; 该酶还可以接受单异戊烯基取代的产物, 催化连续的异戊烯基化反应^[66]。

3 类似萜合酶的aPTs

收起

近期从链霉菌中发现了一类新aPTs, 它们可以催化吲哚类结构单元C-6位的异戊烯基化, 与UbiA型、ABBA型和DMATS型aPTs均无明显的序列相似性, 而与角鲨烯合成酶(squalene synthase) 和八氢番茄红素合酶(phytoene synthase) 具有较高的亲缘性和结构相似性(图 1)。它们也为镁离子依赖型aPTs, 并且具有结合镁离子的特征基序^[69]。S. exfoliatus中的CqsB4^[67]和S. sp. MA37中的NzsG^[68]以DMAPP为异戊烯基供体, 催化三环咔唑(tricyclic carbazole) C-6位的异戊烯基化, 生成carquinostatin和neocarazostatins。S. sp. LHW2432中的LdqG^[69]和S. viridochromogenes 2942-SVS3中的LvqB4^[70]以环薰衣草基(cyclolavandulyl diphosphate, CLPP) 作为异戊烯基供体, 催化三环咔唑C-6位的异戊烯基化, 生成lavanduquinocin。

此外, 有研究发现Alternaria alternata TPF6中的class Ⅰ型倍半萜合酶AaTPS除能将FPP环化成倍半萜烯7-epi-α-selinene外, 在碱性条件下还能在吲哚及其衍生物的N-1和C-3位引入二甲基烯丙基^[71]。AaTPS具有典型的class Ⅰ型萜合酶的结构特点, 也具有结合镁离子的两个富含天冬氨酸的特征基序DDXXD和NSE/DTE。进一步研究表明, class Ⅰ型萜合酶普遍具有异戊烯基化吲哚基团的功能; 其中, F. graminearum中的FgGS不仅接受DMAPP, 还接受GPP作为异戊烯基供体^[71]。

4 总结与展望

收起

PANP类天然产物广泛分布在自然界中, 包括当归、前胡和补骨脂等多种中药材。这类化合物具有多样的生物活性, 展现出很好的成药前景, 并且异戊烯基往往对它们的活性具有重要影响^[2]。在PANP类化合物的生物合成中, aPTs催化异戊烯基取代反应。根据aPTs在亲缘关系、催化机制和结构上的不同, 主要分为膜结合aPTs (UbiA型) 和具有PT桶状结构的可溶性aPTs (包括ABBA型和DMATS型)。此外, 从链霉菌中发现了几个与上述两种类型完全不同的aPTs, 包括CqsB4、NzsG、LdqG和LvqB4。这些酶的发现和表征说明自然界中可能还存在未知类型的aPTs。除aPTs外, 近期还发现class Ⅰ型倍半萜合酶可能普遍具有双重功能, 既能环化FPP又能催化吲哚类结构单元的异戊烯基取代。亲缘关系近的aPTs往往显示出相似的底物偏好性。例如, DMATS型aPTs主要以具有吲哚单元的化合物为异戊烯基的受体, UbiA型aPTs主要以各种多酚类化合物(香豆素、黄酮和醌类等) 为异戊烯基的受体^[3]。

酶法合成及细胞工厂等生物合成技术在天然产物制造方面展现出了巨大潜力^{[86, 87]}。建立生物合成体系的一个重要前提是获得具有优良催化特性(如: 催化效率、底物选择性和稳定性等) 的酶元件。如前所述, 自然界仍然蕴藏着大量未知的aPTs。因此, 挖掘新aPTs的研究将不断丰富该类催化元件。此外, 酶工程技术被广泛地用于天然酶的改造^[88]。aPTs的机制研究将为其酶工程改造提供重要依据。目前, 虽然已经解析了微生物中具有PT桶状结构的可溶性aPTs和UbiA型aPTs的结构, 但是植物中UbiA型aPTs的结构仍然未知, 阻碍了其机制研究。除结构生物学外, 多尺度模拟等计算技术在酶机制研究中也发挥了重要作用^[89], 尤其适用于不可溶的膜蛋白(例如植物中的UbiA型aPTs)。随着更多aPTs机制被阐明, 必将推动其工程化研究。总之, 基于基因挖掘所获得的天然aPTs还是基于酶工程所获得的突变aPTs, 都将促进活性PANP类天然产物的生物合成, 从而为其深入的成药性研究提供保障。

作者贡献: 谢萌负责综述撰写; 潘英妮修改综述; 李宁和訾佳辰提供选题和撰写思路并指导综述修改。

利益冲突: 本文所有作者声明不存在利益冲突关系。

基金

收起

国家自然科学基金重大项目(82293682)
中国医学科学院创新工程项目(2021-I2M-1-029-5)
中国医学科学院基本科研业务费项目(2021-RC350-009)

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

[1]

Wang MH, Zhang KJ, Gu QL, et al. Pharmacology of mangostins and their derivatives: a comprehensive review [J]. Chin J Nat Med, 2017, 15: 81-93.

[2]

Botta B, Delle Monache G, Menendez P, et al. Novel prenyltransferase enzymes as a tool for flavonoid prenylation [J]. Trends Pharmacol Sci, 2005, 26: 606-608.

[3]

An T, Feng XD, Li C. Prenylation: a critical step for biomanufacturing of prenylated aromatic natural products [J]. J Agric Food Chem, 2023, 71: 2211-2233.

[4]

Cheng W, Li WK. Structural insights into ubiquinone biosynthesis in membranes [J]. Science, 2014, 343: 878-881.

[5]

Bonitz T, Alva V, Saleh O, et al. Evolutionary relationships of microbial aromatic prenyltransferases [J]. PLoS One, 2011, 6: e27336.

[6]

Huang H, Levin EJ, Liu S, et al. Structure of a membrane-embedded prenyltransferase homologous to UBIAD1 [J]. PLoS Biol, 2014, 12: e1001911.

[7]

Yang Y, Fu L, Zhang JL, et al. Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318 [J]. PLoS One, 2014, 9: e99537.

[8]

Liu MM, Ma YM, Du Q, et al. Functional analysis of polyprenyl diphosphate synthase genes involved in plastoquinone and ubiquinone biosynthesis in Salvia miltiorrhiza [J]. Front Plant Sci, 2019, 10: 893.

[9]

Wang S, Wang RS, Liu T, et al. Production of 3-geranyl-4-hydroxybenzoate acid in yeast, an important intermediate of shikonin biosynthesis pathway [J]. FEMS Yeast Res, 2017, 17: 1-8.

[10]

Dhiman RK, Pujari V, Kincaid JM, et al. Characterization of MenA (isoprenyl diphosphate: 1, 4-dihydroxy-2-naphthoate isoprenyltransferase) from Mycobacterium tuberculosis [J]. PLoS One, 2019, 14: e0214958.

[11]

Yang SM, Cao YX, Sun LM, et al. Modular pathway engineering of Bacillus subtilis to promote de novo biosynthesis of menaquinone-7 [J]. ACS Synth Biol, 2018, 8: 70-81.

[12]

Liu CZ, Wang RS, Wang S, et al. A prenyltransferase participates in the biosynthesis of anthraquinones in Rubia cordifolia [J]. Plant Physiol, 2024, 195: 2860-2876.

[13]

Nakagawa K, Sawada N, Hirota Y, et al. Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice [J]. PLoS One, 2014, 9: e104078.

[14]

Wunnakup T, Vimolmangkang S, De-Eknamkul W. Transient expression of the homogentisate phytyltransferase gene from Clitoria ternatea causes metabolic enhancement of α-tocopherol biosynthesis and chlorophyll degradation in tomato leaves [J]. J Plant Biochem Biotechnol, 2017, 27: 55-67.

[15]

Zhang YH, Liu K, Zhu XM, et al. Rice tocopherol deficiency 1 encodes a homogentisate phytyltransferase essential for tocopherol biosynthesis and plant development in rice [J]. Plant Cell Rep, 2018, 37: 775-787.

[16]

Li HX, Ban ZN, Qin H, et al. A heteromeric membrane-bound prenyltransferase complex from hop catalyzes three sequential aromatic prenylations in the bitter acid pathway [J]. Plant Physiol, 2015, 167: 650-659.

[17]

Karamat F, Olry A, Munakata R, et al. A coumarin-specific prenyltransferase catalyzes the crucial biosynthetic reaction for furanocoumarin formation in parsley [J]. Plant J, 2014, 77: 627-638.

[18]

Munakata R, Olry A, Karamat F, et al. Molecular evolution of parsnip (Pastinaca sativa) membrane-bound prenyltransferases for linear and/or angular furanocoumarin biosynthesis [J]. New Phytol, 2016, 211: 332-344.

[19]

Wang KX, Zeng HH, Dai YQ, et al. Three types of enzymes complete the furanocoumarins core skeleton biosynthesis in Angelica sinensis [J]. Phytochemistry, 2024, 222: 114102.

[20]

Huang XC, Tang HY, Wei XF, et al. The gradual establishment of complex coumarin biosynthetic pathway in Apiaceae [J]. Nat Commun, 2024, 15: 6864.

[21]

Munakata R, Inoue T, Koeduka T, et al. Molecular cloning and characterization of a geranyl diphosphate-specific aromatic prenyltransferase from lemon [J]. Plant Physiol, 2014, 166: 80-90.

[22]

Munakata R, Kitajima S, Nuttens A, et al. Convergent evolution of the UbiA prenyltransferase family underlies the independent acquisition of furanocoumarins in plants [J]. New Phytol, 2020, 225: 2166-2182.

[23]

Munakata R, Takemura T, Tatsumi K, et al. Isolation of Artemisia capillaris membrane-bound di-prenyltransferase for phenylpropanoids and redesign of artepillin C in yeast [J]. Commun Biol, 2019, 2: 384.

[24]

Munakata R, Olry A, Takemura T, et al. Parallel evolution of UbiA superfamily proteins into aromatic O-prenyltransferases in plants [J]. Proc Natl Acad Sci U S A, 2021, 118: e2022294118.

[25]

Li N, Liu X, Zhang ML, et al. Characterization of a coumarin C-/O-prenyltransferase and a quinolone C-prenyltransferase from Murraya exotica [J]. Org Biomol Chem, 2022, 20: 5535-5542.

[26]

Wang PP, Li CJ, Li XD, et al. Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli [J]. Sci Bull (Beijing), 2021, 66: 1906-1916.

[27]

Shen GA, Luo YJ, Yao Y, et al. The discovery of a key prenyltransferase gene assisted by a chromosome-level Epimedium pubescens genome [J]. Front Plant Sci, 2022, 13: 1034943.

[28]

Liu JY, Xia YY, Jiang WB, et al. LaPT2 gene encodes a flavonoid prenyltransferase in white lupin [J]. Front Plant Sci, 2021, 12: 673337.

[29]

Yang JL, Zhou T, Jiang YM, et al. Substrate specificity change of a flavonoid prenyltransferase AhPT1 induced by metal ion [J]. Int J Biol Macromol, 2020, 153: 264-275.

[30]

Li JH, Chen RD, Wang RS, et al. GuA6DT, a regiospecific prenyltransferase from Glycyrrhiza uralensis, catalyzes the 6-prenylation of flavones [J]. Chembiochem, 2014, 15: 1673-1681.

[31]

Li JH, Chen RD, Wang RS, et al. Biocatalytic access to diverse prenylflavonoids by combining a regiospecific C-prenyltransferase and a stereospecific chalcone isomerase [J]. Acta Pharm Sin B, 2018, 8: 678-686.

[32]

Liu JY, Jiang WB, Xia YY, et al. Genistein-specific G6DT gene for the inducible production of wighteone in Lotus japonicus [J]. Plant Cell Physiol, 2018, 59: 128-141.

[33]

Yoneyama K, Akashi T, Aoki T. Molecular characterization of soybean pterocarpan 2-dimethylallyltransferase in glyceollin biosynthesis: local gene and whole-genome duplications of prenyltransferase genes led to the structural diversity of soybean prenylated isoflavonoids [J]. Plant Cell Physiol, 2016, 57: 2497-2509.

[34]

Sukumaran A, McDowell T, Chen L, et al. Isoflavonoid-specific prenyltransferase gene family in soybean: GmPT01, a pterocarpan 2-dimethylallyltransferase involved in glyceollin biosynthesis [J]. Plant J, 2018, 96: 966-981.

[35]

He JB, Dong ZY, Hu ZM, et al. Regio-specific prenylation of pterocarpans by a membrane-bound prenyltransferase from Psoralea corylifolia [J]. Org Biomol Chem, 2018, 16: 6760-6766.

[36]

Wang Y, Luo Y, Zhang Y, et al. A novel flavonoid prenyltransferase gene PcPT11 with broad substrate promiscuity in Psoralea corylifolia L. [J]. Ind Crops Prod, 2023, 199: 116746.

[37]

Wang RS, Chen RD, Li JH, et al. Molecular characterization and phylogenetic analysis of two novel regio-specific flavonoid prenyltransferases from Morus alba and Cudrania tricuspidata [J]. J Biol Chem, 2014, 289: 35815-35825.

[38]

Zhong ZH, Zhu W, Liu SZ, et al. Molecular characterization of a geranyl diphosphate-specific prenyltransferase catalyzing stilbenoid prenylation from Morus alba [J]. Plant Cell Physiol, 2018, 59: 2214-2227.

[39]

Yang TH, Fang LL, Sanders S, et al. Stilbenoid prenyltransferases define key steps in the diversification of peanut phytoalexins [J]. J Biol Chem, 2018, 293: 28-46.

[40]

Fiesel T, Gaid M, Müller A, et al. Molecular cloning and characterization of a xanthone prenyltransferase from Hypericum calycinum cell cultures [J]. Molecules, 2015, 20: 15616-15630.

[41]

Nagia M, Gaid M, Biedermann E, et al. Sequential regiospecific gem-diprenylation of tetrahydroxyxanthone by prenyltransferases from Hypericum sp. [J]. New Phytol, 2019, 222: 318-334.

[42]

Tanaya R, Kodama T, Lee YE, et al. Catalytic potential of Cannabis prenyltransferase to expand cannabinoid scaffold diversity [J]. Org Lett, 2023, 25: 8601-8605.

[43]

Jordan EN, Schmidt C, Kayser O. Foldseek reveals a CBGA prenylating enzyme GlyMa_02G168000 from Glycine max [J]. Biochem Biophys Res Commun, 2024, 696: 149471.

[44]

Yang ER, Yao YP, Liu YH, et al. A gatekeeper residue controls aromatic acceptor specificity of the PHB-type UbiA prenyltransferases [J]. ACS Catal, 2023, 13: 13717-13728.

[45]

Amiri Moghaddam J, Guo HJ, Willing K, et al. Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity [J]. Beilstein J Org Chem, 2022, 18: 722-731.

[46]

Yu XT, Ma CT, Wang WX, et al. Genome mining reveals a UbiA-type prenyltransferase access to farnesylation of diketopiperazines [J]. Org Lett, 2024, 26: 3349-3354.

[47]

Zeyhle P, Bauer JS, Kalinowski J, et al. Genome-based discovery of a novel membrane-bound 1, 6-dihydroxyphenazine prenyltransferase from a marine actinomycete [J]. PLoS One, 2014, 9: e99122.

[48]

Zeyhle P, Bauer JS, SteimLe M, et al. A membrane-bound prenyltransferase catalyzes the O-prenylation of 1, 6-dihydroxyphenazine in the marine bacterium Streptomyces sp. CNQ-509 [J]. Chembiochem, 2014, 15: 2385-2392.

[49]

Zhang KJ, Zhang GJ, Hou XW, et al. A fungal promiscuous UbiA prenyltransferase expands the structural diversity of chrodrimanin-type meroterpenoids [J]. Org Lett, 2022, 24: 2025-2029.

[50]

Chen XW, Wang L, Zhang JM, et al. Immunosuppressant mycophenolic acid biosynthesis employs a new globin-like enzyme for prenyl side chain cleavage [J]. Acta Pharm Sin B, 2019, 9: 1253-1258.

[51]

Bai N, Li GH, Luo SL, et al. Vib-PT, an aromatic prenyltransferase involved in the biosynthesis of vibralactone from Stereum vibrans [J]. Appl Environ Microbiol, 2020, 86: e02687-19.

[52]

Wang J, Chen CC, Yang YY, et al. Structural insight into a novel indole prenyltransferase in hapalindole-type alkaloid biosynthesis [J]. Biochem Biophys Res Commun, 2018, 495: 1782-1788.

[53]

Hillwig ML, Zhu Q, Liu XY. Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua [J]. ACS Chem Biol, 2014, 9: 372-377.

[54]

Leipoldt F, Zeyhle P, Kulik A, et al. Diversity of ABBA prenyltransferases in marine Streptomyces sp. CNQ-509: promiscuous enzymes for the biosynthesis of mixed terpenoid compounds [J]. PLoS One, 2015, 10: e0143237.

[55]

Qiu C, Liu Y, Wu YB, et al. Biochemical characterization of a novel prenyltransferase from Streptomyces sp. NT11 and development of a recombinant strain for the production of 6-prenylnaringenin [J]. J Agric Food Chem, 2021, 69: 14231-14240.

[56]

Miyamoto K, Ishikawa F, Nakamura S, et al. A 7-dimethylallyl tryptophan synthase from a fungal Neosartorya sp. : biochemical characterization and structural insight into the regioselective prenylation [J]. Bioorg Med Chem, 2014, 22: 2517-2528.

[57]

Wohlgemuth V, Kindinger F, Xie XL, et al. Two prenyltransferases govern a consecutive prenylation cascade in the biosynthesis of echinulin and neoechinulin [J]. Org Lett, 2017, 19: 5928-5931.

[58]

Winkelblech J, Li SM. Biochemical investigations of two 6-DMATS enzymes from Streptomyces reveal new features of L-tryptophan prenyltransferases [J]. Chembiochem, 2014, 15: 1030-1039.

[59]

Elshahawi SI, Cao HN, Shaaban KA, et al. Structure and specificity of a permissive bacterial C-prenyltransferase [J]. Nat Chem Biol, 2017, 13: 366-368.

[60]

Roose BW, Christianson DW. Structural basis of tryptophan reverse N-prenylation catalyzed by CymD [J]. Biochemistry, 2019, 58: 3232-3242.

[61]

Awakawa T, Zhang LH, Wakimoto T, et al. A methyltransferase initiates terpene cyclization in teleocidin B biosynthesis [J]. J Am Chem Soc, 2014, 136: 9910-9913.

[62]

Fan AL, Chen HZ, Wu R, et al. A new member of the DMATS superfamily from Aspergillus niger catalyzes prenylations of both tyrosine and tryptophan derivatives [J]. Appl Microbiol Biotechnol, 2014, 98: 10119-10129.

[63]

Arndt B, Janevska S, Schmid R, et al. A fungal N-dimethylallyltryptophan metabolite from Fusarium fujikuroi [J]. Chembiochem, 2017, 18: 899-904.

[64]

Chunkrua P, Leschonski KP, Gran-Scheuch AA, et al. Prenylation of aromatic amino acids and plant phenolics by an aromatic prenyltransferase from Rasamsonia emersonii [J]. Appl Microbiol Biotechnol, 2024, 108: 421.

[65]

He J, Hu Z, Dong Z, et al. Enzymatic O-prenylation of diverse phenolic compounds by a permissive O-prenyltransferase from the medicinal mushroom Antrodia camphorata [J]. Adv Synth Catal, 2020, 362: 528-532.

[66]

Chen RD, Gao BQ, Liu X, et al. Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase [J]. Nat Chem Biol, 2017, 13: 226-234.

[67]

Kobayashi M, Tomita T, Shin-Ya K, et al. An unprecedented cyclization mechanism in the biosynthesis of carbazole alkaloids in Streptomyces [J]. Angew Chem Int Ed Engl, 2019, 58: 13349-13353.

[68]

Huang S, Elsayed SS, Lv MN, et al. Biosynthesis of neocarazostatin a reveals the sequential carbazole prenylation and hydroxylation in the tailoring steps [J]. Chem Biol, 2015, 22: 1633-1642.

[69]

Shen YY, Zhang L, Yang M, et al. Switching prenyl donor specificities in squalene synthase-like aromatic prenyltransferases from bacterial carbazole alkaloid biosynthesis [J]. ACS Chem Biol, 2023, 18: 123-133.

[70]

Nagata R, Suemune H, Kobayashi M, et al. Structural basis for the prenylation reaction of carbazole-containing natural products catalyzed by squalene synthase-like enzymes [J]. Angew Chem Int Ed Engl, 2022, 61: e202117430.

[71]

He HB, Bian GK, Herbst-Gervasoni CJ, et al. Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases [J]. Nat Commun, 2020, 11: 3958.

[72]

Li WK. Bringing bioactive compounds into membranes: the UbiA superfamily of intramembrane aromatic prenyltransferases [J]. Trends Biochem Sci, 2016, 41: 356-370.

[73]

Forsgren M, Attersand A, Lake S, et al. Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ [J]. Biochem J, 2004, 382: 519-526.

[74]

Parrado-Fernández C, López-Lluch G, Rodríguez-Bies E, et al. Calorie restriction modifies ubiquinone and CoQ transcript levels in mouse tissues [J]. Free Radic Biol Med, 2011, 50: 1728-1736.

[75]

Nakagawa K, Hirota Y, Sawada N, et al. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme [J]. Nature, 2010, 468: 117-121.

[76]

Suvarna K, Stevenson D, Meganathan R, et al. Menaquinone (vitamin K2) biosynthesis: localization and characterization of the MenA gene from Escherichia coli [J]. J Bacteriol, 1998, 180: 2782-2787.

[77]

Mugoni V, Postel R, Catanzaro V, et al. UBIAD1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis [J]. Cell, 2013, 152: 504-518.

[78]

Kim HJ, Khalimonchuk O, Smith PM, et al. Structure, function, and assembly of heme centers in mitochondrial respiratory complexes [J]. Biochim Biophys Acta, 2012, 1823: 1604-1616.

[79]

Mogi T. Over-expression and characterization of Bacillus subtilis heme O synthase [J]. J Biochem, 2009, 145: 669-675.

[80]

Luo YJ, Wang YY, Pang YZ, et al. Research progress of UbiA membrane-bound aromatic prenyltransferases in plants [J]. Plant Sci J (植物科学学报), 2023, 41: 256-268.

[81]

Wu ZM, Zhang X, He B, et al. A chlorophyll-deficient rice mutant with impaired chlorophyllide esterification in chlorophyll biosynthesis [J]. Plant Physiol, 2007, 145: 29-40.

[82]

Metzger U, Schall C, Zocher G, et al. The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria [J]. Proc Natl Acad Sci U S A, 2009, 106: 14309-14314.

[83]

Tello M, Kuzuyama T, Heide L, et al. The ABBA family of aromatic prenyltransferases: broadening natural product diversity [J]. Cell Mol Life Sci, 2008, 65: 1459-1463.

[84]

Kuzuyama T, Noel JP, Richard SB. Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products [J]. Nature, 2005, 435: 983-987.

[85]

Mori T, Zhang LH, Awakawa T, et al. Manipulation of prenylation reactions by structure-based engineering of bacterial indolactam prenyltransferases [J]. Nat Commun, 2016, 7: 10849.

[86]

Liu PT, Zhang YF, Liu Y, et al. Study on the catalytic mechanism of triterpene C-29 carboxylases from Tripterygium wilfordii based on directed evolution [J]. Acta Pharm Sin (药学学报), 2024, 59: 1883-1893.

[87]

Sun XY, Chen JJ, Chen TJ, et al. Research progress on protein engineering technology and its application in the synthesis biology of medicinal natural products [J]. Acta Pharm Sin (药学学报), 2024, 59: 1601-1615.

[88]

Pan YJ, Li GB, Liu RX, et al. Unnatural activities and mechanistic insights of cytochrome P450 PikC gained from site-specific mutagenesis by non-canonical amino acids [J]. Nat Commun, 2023, 14: 1669.

[89]

Tian WS, Yan YR, Cui XX, et al. Gene cloning, functional identification, structural and expression analysis of sucrose synthase from Cistanche tubulosa [J]. Acta Pharm Sin (药学学报), 2024, 59: 3153-3163.

2025年第60卷第3期

PDF下载

176

引用本文

BibTeX

文章信息

doi: 10.16438/j.0513-4870.2024-1067

接收时间：2024-09-10
首发时间：2025-11-06
出版时间：2025-03-12

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2024-09-10
修回日期：2025-02-18

基金

国家自然科学基金重大项目(82293682)

中国医学科学院创新工程项目(2021-I2M-1-029-5)

中国医学科学院基本科研业务费项目(2021-RC350-009)

作者信息

1.沈阳药科大学中药学院, 辽宁省重大慢病中药创新药重点实验室, 沈阳市中药药效物质研究与创新药开发重点实验室, 辽宁沈阳 110016

通讯作者:

^*李宁, Tel: 86-24-43520739, E-mail: liningsypharm@163.com

訾佳辰, Tel: 86-10-50927375, E-mail: zijiachen@imm.ac.cn

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/yxxb/CN/10.16438/j.0513-4870.2024-1067

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

关闭全屏

BibTeX
EndNote
RefWorks
TxT

Type	Protein	Species	Prenyl donor	Substrate	Prenyl substitution site	Ref.
Membrane-bound UbiA type aPTs	AfUbiA	Archaeoglobus fulgidus	FPP, GPP, GGPP	PHB	C-3	[6]
	XimB	Streptomyces xiamenensis 318	FPP, GPP, GGPP	PHB	C-3	[7]
	SmPPT	Salvia miltiorrhiza Bunge	Polyprenyl-PP	PHB	C-3	[8]
	AePGT	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	AePGT4	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	AePGT6	Arnebia euchroma (Royle) Johnst.	GPP	PHB	C-3	[9]
	MtMenA	Mycobacterium tuberculosis	FPP, polyprenyl-PP	DHNA	C-3	[10]
	BsMenA	Bacillus subtilis	FPP, GPP, GGPP, polyprenyl-PP	DHNA	C-3	[11]
	RcDT1	Rubia cordifolia L.	DMAPP	DHNA	C-3	[12]
	MmUBIAD1	Mus musculus	GGPP	Menadione	C-3	[13]
	CtHPT	Clitoria ternatea L.	PDP	HGA	C-3	[14]
	RTD1	Oryza sativa L.	PDP	HGA	C-3	[15]
	HlPT1L	Humulus lupulus L.	SDP	HGA	C-3	[16]
	HlPT2	Humulus lupulus L.	SDP	HGA	C-3	[16]
	PcPT	Petroselinum crispum (Mill.) Hill	DMAPP	Umbelliferone	C-6, C-8	[17]
	PsPT1	Pastinaca sativa L.	DMAPP	Umbelliferone	C-6	[18]
	PsPT2	Pastinaca sativa L.	DMAPP	Umbelliferone	C-8	[18]
	AsPT1	Angelica sinensis (Oliv.) Diels	DMAPP	Umbelliferone	C-6	[19]
	AsPT2	Angelica sinensis (Oliv.) Diels	DMAPP	Umbelliferone	C-8	[19]
	PpPT1	Peucedanum praeruptorum Dunn	DMAPP	Umbelliferone	C-6	[20]
	PpPT2	Peucedanum praeruptorum Dunn	DMAPP	Umbelliferone	C-8	[20]
	ClPT1	Citrus limon (L.) Burm. F.	GPP	Umbelliferone, esculetine, 5, 7-dihydroxycoumarin, 5-methoxy-7-hydroxycoumarin	C-8	[21]
	FcPT1a	Ficus carica Linn.	DMAPP	Umbelliferone, 5-methoxy-7-hydroxycoumarin	C-6	[22]
	FcPT1b	Ficus carica Linn.	DMAPP	Umbelliferone	C-6	[22]
	AcPT1	Artemisia capillaris Thunb.	DMAPP, GPP	p-Coumaric acid, ferulate, drupanin	C-3, C-5	[23]
	CpPT1	Citrus paradisi Macf.	GPP	5, 7-Dihydroxycoumarin, 5-hydroxy-7-methoxycoumarin, xanthotoxol, bergaptol, 8-hydroxybergapten	5-OH, 8-OH	[24]
	AkPT1	Angelica keiskei Koidz.	DMAPP	Bergaptol, xanthotoxol	C-5, C-8	[24]
	MePT1	Murraya exotica L.	GPP	Umbelliferone	C-6, C-8, 7-OH	[25]
	EsPT2	Epimedium sagittatum (Sieb. et Zucc.) Maxim.	DMAPP	Kaempferol, kaempferide, naringenin	C-8	[26]
	EpPT8	Epimedium pubescens Maxim.	DMAPP	Kaempferol, quercetin, apigenin	C-8	[27]
	LaPT2	Lupinus albus L.	DMAPP	Kaempferol, quercetin, fisetin, galangin, myricetin, naringenin	C-8	[28]
	AhPT1	Artocarpus heterophyllus Lam.	DMAPP	Genistein, 6-hydroxyflavone, etc.	C-6, C-5	[29]
	GuA6DT	Glycyrrhiza uralensis Fisch.	DMAPP, GPP	Apigenin, chrysin, luteolin, etc.	C-6	[30]
	GuILDT	Glycyrrhiza uralensis Fisch.	DMAPP	Naringenin chalcone, 2′, 4′-dihydroxychalcone, etc.	C-3′	[31]
	LjG6DT	Lotus corniculatus L.	DMAPP	Genistein	C-6	[32]
	GmIDT1	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	B-ring	[33]
	GmIDT2	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	A-ring	[33]
	GmPT3	Glycine max (L.) Merr.	DMAPP	Daidzein, genistein	Unknown	[33]
	GmC4DT	Glycine max (L.) Merr.	DMAPP	Coumestrol	C-4	[33]
	GmG2DT	Glycine max (L.) Merr.	DMAPP	Glycinol	C-2	[33]
	GmPT01	Glycine max (L.) Merr.	DMAPP	Glycinol	C-2	[34]
	PcM4DT	Psoralea corylifolia Linn.	DMAPP	Maackiain, medicarpin	C-4	[35]
	PcPT11	Psoralea corylifolia Linn.	DMAPP	Genistein, apigenin, isorhamnetin, etc.	C-6	[36]
	MaIDT	Morus alba L.	DMAPP, GPP	Genistein, isoliquiritigenin, apigenin, etc.	C-3′	[37]
	CtIDT	Cudrania tricuspidata (Carr.) Bur.	DMAPP, GPP	Genistein, isoliquiritigenin, etc.	C-4′	[37]
	MaOGT	Morus alba L.	GPP, IPP, DMAPP, FPP, GGPP	Oxyresveratrol, resveratrol	C-4	[38]
	AhR4DT-1	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol, pinosylvin	C-4	[39]
	AhR3′DT-1	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-2	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-3	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	AhR3′DT-4	Arachis hypogaea L.	DMAPP	Oxyresveratrol, piceatannol	C-3′	[39]
	HcPT	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 7-trihydroxyxanthone, 1, 3, 5, 6-tetrahydroxyxanthone	C-8	[40]
	HcPT8px	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone	C-8	[41]
	HcPT8pat	Hypericum calycinum L.	DMAPP	1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone	C-8	[41]
	HsPT8px	Hypericum sampsonii Hance	DMAPP	1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 6, 7-tetrahydroxy-8-prenylxanthone	C-8	[41]
	HsPT8pat	Hypericum sampsonii Hance	DMAPP	1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone	C-8	[41]
	CsPT4	Cannabis sativa L.	DMAPP, GPP, FPP, GGPP	OA, etc.	C-3	[42]
	GlyMa_02G168000	Glycine max (L.) Merr.	DMAPP	OA	C-3	[43]
	MePT2	Murraya exotica L.	DMAPP	Quinolone	C-3	[25]
	ClaS	Clitocybe clavipes	GPP	Hydroquinone	C-2	[44]
	UbiA-297	Maribacter sp. MS6	FPP	8-Hydroxyquinoline-2-carboxylic acid, quinaldic acid, 1, 3-dihydroxynaphthalene, etc.	Unknown	[45]
	FtaB	Talaromyces variabilis H1	FPP	Indole-containing diketopiperazines	C-2	[46]
	Mpz10	Streptomyces sp.	DMAPP	1-Hydroxyphenazine, 1, 6-dihydroxyphenazine	C-4, C-9	[47]
	CnqPT1	Streptomyces sp. CNQ-509	GPP, DMAPP, FPP	1, 6-Dihydroxyphenazine, 1-hydroxyphenazine, flaviolin	1-OH, 2-OH	[48]
	CdnC	Penicillium funiculosum GWT2-24	FPP	Benzo-pyranone, benzo-cyclohexanone, etc.	C-5	[49]
	PgMpaA	Penicillium brevicompactum	FPP, GPP	5, 7-Dihydroxy-4-methylphthalde	C-6	[50]
ABBA type aPTs	Vib-PT	Stereum vibrans	DMAPP, GPP, FPP, GGPP	4-Hydroxybenzyl alcohol, 4-hydroxybenzaldehyde, etc.	3-OH, 4-OH, C-3	[51]
	AmbP3	Fischerella ambigua UTEX1903	DMAPP, GPP	cis-Indole nitrile, hapalindole U, hapalindole G, hapalindole A	C-2, C-3	[52, 53]
	FamD2	Fischerella ambigua UTEX1903	DMAPP, GPP	cis-Indole nitrile	C-2, C-3	[52]
	CnqP2	Streptomyces sp. CNQ-509	GPP, DMAPP	Genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene	7-OH, C-5, C-1	[54]
	CnqP3	Streptomyces sp. CNQ-509	GPP, DMAPP	Flaviolin, genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene	7-OH, C-5, C-1	[54]
	CnqP4	Streptomyces sp. CNQ-509	GPP	2, 7-Dihydroxynaphthalene	C-1	[54]
	CnqP5	Streptomyces sp. CNQ-509	DMAPP	1, 6-Dihydroxynaphthalene	C-5	[54]
	CnqP6	Streptomyces sp. CNQ-509	GPP	Genistein	7-OH	[54]
	ShFPT	Streptomyces sp. NT11	DMAPP	Naringenin	C-6	[55]
DMATS type aPTs	7-DMATS	Neosartorya sp.	DMAPP	L-Tryptophan, simple indole derivatives	C-7	[56]
	EchPT1	Aspergillus ruber CBS 135680	DMAPP	cyclo-L-Trp-L-Ala	C-2	[57]
	EchPT2	Aspergillus ruber CBS 135680	DMAPP	Preechinulin, etc.	Unknown	[57]
	SAML0654	Streptomyces ambofaciens	DMAPP, GPP	Tryptophan, tryptophan derivatives, naphthol, etc.	C-6	[58]
	Strvi8510	Streptomyces violaceusniger	DMAPP, GPP	Tryptophan, tryptophan derivatives, naphthol, etc.	C-6	[58]
	PriB	Streptomyces sp. RM-5-8	DMAPP, GPP, FPP, etc.	L-Tryptophan, simple indole derivatives, naphthol, anthraquinone, etc.	C-6	[59]
	CymD	Salinispora arenicola CNS-205	DMAPP	L-Tryptophan, indole, indole-like small molecules	N-1	[60]
	TleC	Streptomyces blastmyceticus NBRC 12747	GPP	Indolactam V	C-7	[61]
	TyrPT	Aspergillus niger	DMAPP	Tyrosine, tyrosine derivatives, tryptophan, tryptophan derivatives	4-OH, C-7	[62]
	DMATS1	Fusarium fujikuroi	DMAPP	L-Tryptophan	N-1	[63]
	RePT	Rasamsonia emersonii	DMAPP, GPP	L-Tryptophan, L-tyrosine, flavonoids, coumarins, etc.	C-7, N-1, etc.	[64]
	AcaPT	Taiwanofungus camphoratus	DMAPP	L-Tryptophan, flavonoids, coumarins, etc.	4'-OH, 7-OH, etc.	[65]
	AtaPT	Aspergillus terreus	DMAPP, GPP, FPP	Tryptophan derivatives, flavonoids, coumarins, etc.	C-3', C-4', C-6	[66]
Terpene cyclase-like aPTs	CqsB4	Streptomyces exfoliatus	DMAPP	Tricyclic carbazole	C-6	[67]
	NzsG	Streptomyces sp. MA37	DMAPP	Tricyclic carbazole	C-6	[68]
	LdqG	Streptomyces sp. LHW2432	CLPP	Tricyclic carbazole	C-6	[69]
	LvqB4	Streptomyces viridochromogenes 2942-SVS3	CLPP	Tricyclic carbazole	C-6	[70]
	AaTPS	Alternaria alternata TPF6	DMAPP	Indole, indole derivatives	N-1, C-3	[71]
	FgGS	Fusarium graminearum	DMAPP, GPP	Indole, indole derivatives	N-1, C-3	[71]

Type

Protein

Species

Prenyl donor

Substrate

Prenyl substitution site

Ref.

Membrane-bound UbiA type aPTs

AfUbiA

Archaeoglobus fulgidus

FPP, GPP, GGPP

PHB

C-3

[6]

XimB

Streptomyces xiamenensis 318

FPP, GPP, GGPP

PHB

C-3

[7]

SmPPT

Salvia miltiorrhiza Bunge

Polyprenyl-PP

PHB

C-3

[8]

AePGT

Arnebia euchroma (Royle) Johnst.

GPP

PHB

C-3

[9]

AePGT4

Arnebia euchroma (Royle) Johnst.

GPP

PHB

C-3

[9]

AePGT6

Arnebia euchroma (Royle) Johnst.

GPP

PHB

C-3

[9]

MtMenA

Mycobacterium tuberculosis

FPP, polyprenyl-PP

DHNA

C-3

[10]

BsMenA

Bacillus subtilis

FPP, GPP, GGPP, polyprenyl-PP

DHNA

C-3

[11]

RcDT1

Rubia cordifolia L.

DMAPP

DHNA

C-3

[12]

MmUBIAD1

Mus musculus

GGPP

Menadione

C-3

[13]

CtHPT

Clitoria ternatea L.

PDP

HGA

C-3

[14]

RTD1

Oryza sativa L.

PDP

HGA

C-3

[15]

HlPT1L

Humulus lupulus L.

SDP

HGA

C-3

[16]

HlPT2

Humulus lupulus L.

SDP

HGA

C-3

[16]

PcPT

Petroselinum crispum (Mill.) Hill

DMAPP

Umbelliferone

C-6, C-8

[17]

PsPT1

Pastinaca sativa L.

DMAPP

Umbelliferone

C-6

[18]

PsPT2

Pastinaca sativa L.

DMAPP

Umbelliferone

C-8

[18]

AsPT1

Angelica sinensis (Oliv.) Diels

DMAPP

Umbelliferone

C-6

[19]

AsPT2

Angelica sinensis (Oliv.) Diels

DMAPP

Umbelliferone

C-8

[19]

PpPT1

Peucedanum praeruptorum Dunn

DMAPP

Umbelliferone

C-6

[20]

PpPT2

Peucedanum praeruptorum Dunn

DMAPP

Umbelliferone

C-8

[20]

ClPT1

Citrus limon (L.) Burm. F.

GPP

Umbelliferone, esculetine, 5, 7-dihydroxycoumarin, 5-methoxy-7-hydroxycoumarin

C-8

[21]

FcPT1a

Ficus carica Linn.

DMAPP

Umbelliferone, 5-methoxy-7-hydroxycoumarin

C-6

[22]

FcPT1b

Ficus carica Linn.

DMAPP

Umbelliferone

C-6

[22]

AcPT1

Artemisia capillaris Thunb.

DMAPP, GPP

p-Coumaric acid, ferulate, drupanin

C-3, C-5

[23]

CpPT1

Citrus paradisi Macf.

GPP

5, 7-Dihydroxycoumarin, 5-hydroxy-7-methoxycoumarin, xanthotoxol, bergaptol, 8-hydroxybergapten

5-OH, 8-OH

[24]

AkPT1

Angelica keiskei Koidz.

DMAPP

Bergaptol, xanthotoxol

C-5, C-8

[24]

MePT1

Murraya exotica L.

GPP

Umbelliferone

C-6, C-8, 7-OH

[25]

EsPT2

Epimedium sagittatum (Sieb. et Zucc.) Maxim.

DMAPP

Kaempferol, kaempferide, naringenin

C-8

[26]

EpPT8

Epimedium pubescens Maxim.

DMAPP

Kaempferol, quercetin, apigenin

C-8

[27]

LaPT2

Lupinus albus L.

DMAPP

Kaempferol, quercetin, fisetin, galangin, myricetin, naringenin

C-8

[28]

AhPT1

Artocarpus heterophyllus Lam.

DMAPP

Genistein, 6-hydroxyflavone, etc.

C-6, C-5

[29]

GuA6DT

Glycyrrhiza uralensis Fisch.

DMAPP, GPP

Apigenin, chrysin, luteolin, etc.

C-6

[30]

GuILDT

Glycyrrhiza uralensis Fisch.

DMAPP

Naringenin chalcone, 2′, 4′-dihydroxychalcone, etc.

C-3′

[31]

LjG6DT

Lotus corniculatus L.

DMAPP

Genistein

C-6

[32]

GmIDT1

Glycine max (L.) Merr.

DMAPP

Daidzein, genistein

B-ring

[33]

GmIDT2

Glycine max (L.) Merr.

DMAPP

Daidzein, genistein

A-ring

[33]

GmPT3

Glycine max (L.) Merr.

DMAPP

Daidzein, genistein

Unknown

[33]

GmC4DT

Glycine max (L.) Merr.

DMAPP

Coumestrol

C-4

[33]

GmG2DT

Glycine max (L.) Merr.

DMAPP

Glycinol

C-2

[33]

GmPT01

Glycine max (L.) Merr.

DMAPP

Glycinol

C-2

[34]

PcM4DT

Psoralea corylifolia Linn.

DMAPP

Maackiain, medicarpin

C-4

[35]

PcPT11

Psoralea corylifolia Linn.

DMAPP

Genistein, apigenin, isorhamnetin, etc.

C-6

[36]

MaIDT

Morus alba L.

DMAPP, GPP

Genistein, isoliquiritigenin, apigenin, etc.

C-3′

[37]

CtIDT

Cudrania tricuspidata (Carr.) Bur.

DMAPP, GPP

Genistein, isoliquiritigenin, etc.

C-4′

[37]

MaOGT

Morus alba L.

GPP, IPP, DMAPP, FPP, GGPP

Oxyresveratrol, resveratrol

C-4

[38]

AhR4DT-1

Arachis hypogaea L.

DMAPP

Oxyresveratrol, piceatannol, pinosylvin

C-4

[39]

AhR3′DT-1

Arachis hypogaea L.

DMAPP

Oxyresveratrol, piceatannol

C-3′

[39]

AhR3′DT-2

Arachis hypogaea L.

DMAPP

Oxyresveratrol, piceatannol

C-3′

[39]

AhR3′DT-3

Arachis hypogaea L.

DMAPP

Oxyresveratrol, piceatannol

C-3′

[39]

AhR3′DT-4

Arachis hypogaea L.

DMAPP

Oxyresveratrol, piceatannol

C-3′

[39]

HcPT

Hypericum calycinum L.

DMAPP

1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 7-trihydroxyxanthone, 1, 3, 5, 6-tetrahydroxyxanthone

C-8

[40]

HcPT8px

Hypericum calycinum L.

DMAPP

1, 3, 6, 7-Tetrahydroxyxanthone

C-8

[41]

HcPT8pat

Hypericum calycinum L.

DMAPP

1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone

C-8

[41]

HsPT8px

Hypericum sampsonii Hance

DMAPP

1, 3, 6, 7-Tetrahydroxyxanthone, 1, 3, 6, 7-tetrahydroxy-8-prenylxanthone

C-8

[41]

HsPT8pat

Hypericum sampsonii Hance

DMAPP

1, 3, 6, 7-Tetrahydroxy-8-prenylxanthone

C-8

[41]

CsPT4

Cannabis sativa L.

DMAPP, GPP, FPP, GGPP

OA, etc.

C-3

[42]

GlyMa_02G168000

Glycine max (L.) Merr.

DMAPP

C-3

[43]

MePT2

Murraya exotica L.

DMAPP

Quinolone

C-3

[25]

ClaS

Clitocybe clavipes

GPP

Hydroquinone

C-2

[44]

UbiA-297

Maribacter sp. MS6

FPP

8-Hydroxyquinoline-2-carboxylic acid, quinaldic acid, 1, 3-dihydroxynaphthalene, etc.

Unknown

[45]

FtaB

Talaromyces variabilis H1

FPP

Indole-containing diketopiperazines

C-2

[46]

Mpz10

Streptomyces sp.

DMAPP

1-Hydroxyphenazine, 1, 6-dihydroxyphenazine

C-4, C-9

[47]

CnqPT1

Streptomyces sp. CNQ-509

GPP, DMAPP, FPP

1, 6-Dihydroxyphenazine, 1-hydroxyphenazine, flaviolin

1-OH, 2-OH

[48]

CdnC

Penicillium funiculosum GWT2-24

FPP

Benzo-pyranone, benzo-cyclohexanone, etc.

C-5

[49]

PgMpaA

Penicillium brevicompactum

FPP, GPP

5, 7-Dihydroxy-4-methylphthalde

C-6

[50]

ABBA type aPTs

Vib-PT

Stereum vibrans

DMAPP, GPP, FPP, GGPP

4-Hydroxybenzyl alcohol, 4-hydroxybenzaldehyde, etc.

3-OH, 4-OH, C-3

[51]

AmbP3

Fischerella ambigua UTEX1903

DMAPP, GPP

cis-Indole nitrile, hapalindole U, hapalindole G, hapalindole A

C-2, C-3

[52, 53]

FamD2

Fischerella ambigua UTEX1903

DMAPP, GPP

cis-Indole nitrile

C-2, C-3

[52]

CnqP2

Streptomyces sp. CNQ-509

GPP, DMAPP

Genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene

7-OH, C-5, C-1

[54]

CnqP3

Streptomyces sp. CNQ-509

GPP, DMAPP

Flaviolin, genistein, 1, 6-dihydroxynaphthalene, 2, 7-dihydroxynaphthalene

7-OH, C-5, C-1

[54]

CnqP4

Streptomyces sp. CNQ-509

GPP

2, 7-Dihydroxynaphthalene

C-1

[54]

CnqP5

Streptomyces sp. CNQ-509

DMAPP

1, 6-Dihydroxynaphthalene

C-5

[54]

CnqP6

Streptomyces sp. CNQ-509

GPP

Genistein

7-OH

[54]

ShFPT

Streptomyces sp. NT11

DMAPP

Naringenin

C-6

[55]

DMATS type aPTs

7-DMATS

Neosartorya sp.

DMAPP

L-Tryptophan, simple indole derivatives

C-7

[56]

EchPT1

Aspergillus ruber CBS 135680

DMAPP

cyclo-L-Trp-L-Ala

C-2

[57]

EchPT2

Aspergillus ruber CBS 135680

DMAPP

Preechinulin, etc.

Unknown

[57]

SAML0654

Streptomyces ambofaciens

DMAPP, GPP

Tryptophan, tryptophan derivatives, naphthol, etc.

C-6

[58]

Strvi8510

Streptomyces violaceusniger

DMAPP, GPP

Tryptophan, tryptophan derivatives, naphthol, etc.

C-6

[58]

PriB

Streptomyces sp. RM-5-8

DMAPP, GPP, FPP, etc.

L-Tryptophan, simple indole derivatives, naphthol, anthraquinone, etc.

C-6

[59]

CymD

Salinispora arenicola CNS-205

DMAPP

L-Tryptophan, indole, indole-like small molecules

N-1

[60]

TleC

Streptomyces blastmyceticus NBRC 12747

GPP

Indolactam V

C-7

[61]

TyrPT

Aspergillus niger

DMAPP

Tyrosine, tyrosine derivatives, tryptophan, tryptophan derivatives

4-OH, C-7

[62]

DMATS1

Fusarium fujikuroi

DMAPP

L-Tryptophan

N-1

[63]

RePT

Rasamsonia emersonii

DMAPP, GPP

L-Tryptophan, L-tyrosine, flavonoids, coumarins, etc.

C-7, N-1, etc.

[64]

AcaPT

Taiwanofungus camphoratus

DMAPP

L-Tryptophan, flavonoids, coumarins, etc.

4'-OH, 7-OH, etc.

[65]

AtaPT

Aspergillus terreus

DMAPP, GPP, FPP

Tryptophan derivatives, flavonoids, coumarins, etc.

C-3', C-4', C-6

[66]

Terpene cyclase-like aPTs

CqsB4

Streptomyces exfoliatus

DMAPP

Tricyclic carbazole

C-6

[67]

NzsG

Streptomyces sp. MA37

DMAPP

Tricyclic carbazole

C-6

[68]

LdqG

Streptomyces sp. LHW2432

CLPP

Tricyclic carbazole

C-6

[69]

LvqB4

Streptomyces viridochromogenes 2942-SVS3

CLPP

Tricyclic carbazole

C-6

[70]

AaTPS

Alternaria alternata TPF6

DMAPP

Indole, indole derivatives

N-1, C-3

[71]

FgGS

Fusarium graminearum

DMAPP, GPP

Indole, indole derivatives

N-1, C-3

[71]