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Advances in peptidyl Asx-specific ligases for the application of cyclic peptides
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Xin SHEN, Min-zhi LIU, Yan YANG, Wei WANG*
Acta Pharmaceutica Sinica | 2023, 58(9) : 2656 - 2668
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Acta Pharmaceutica Sinica | 2023, 58(9): 2656-2668
Advances in peptidyl Asx-specific ligases for the application of cyclic peptides
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Xin SHEN, Min-zhi LIU, Yan YANG, Wei WANG*
Affiliations
  • State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Natural Drug Biosynthesis, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Published: 2023-09-12 doi: 10.16438/j.0513-4870.2023-0341
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Asparaginyl endopeptidases (AEPs) in plants belong to the family of cysteine protease that undergo self-activation in the form of zymogen in acidic vacuole and play important physiological roles in maturation of seed storage proteins, protein degradation, programmed cell death and host defense. Bioprocessing enzymes (peptidyl Asx-specific ligases, PALs) that promote the maturation of cyclotides have recently been isolated and identified from several cyclotide-rich plants. PALs derived from AEPs can site-specifically catalyze the formation of asparagine or aspartate peptide bonds. Due to the advantages of relatively traceless peptide bonds and broad substrate spectrum and high catalytic efficiency, they have been playing important roles in the cyclization and modification of peptides and proteins, and are powerful tools for improving the stability of peptide drugs. This review describes the physiological functions of AEPs in plants and summarizes the discoveries, structural characteristics, catalytic mechanism and protein engineering of PALs, as well as the limitation of their applications and future trends. In addition, the applications of PALs in cyclotides biosynthesis and the development of macrocyclic peptides are highlighted, with the aim of providing a new idea for the biocatalytic synthesis of cyclic peptides.

asparaginyl endopeptidase  /  peptidyl Asx-specific ligase  /  cyclic peptide  /  enzymatic cyclization  /  site-specific ligation
Xin SHEN, Min-zhi LIU, Yan YANG, Wei WANG. Advances in peptidyl Asx-specific ligases for the application of cyclic peptides[J]. Acta Pharmaceutica Sinica, 2023 , 58 (9) : 2656 -2668 . DOI: 10.16438/j.0513-4870.2023-0341
Year 2023 volume 58 Issue 9
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doi: 10.16438/j.0513-4870.2023-0341
  • Receive Date:2023-03-22
  • Online Date:2025-11-21
  • Published:2023-09-12
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  • Received:2023-03-22
  • Revised:2023-05-05
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    State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Natural Drug Biosynthesis, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

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
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