Full
Outline
Steroids are the second-largest category of clinical drugs following antibiotics, with significant physiological functions such as anti-inflammatory, antiviral, antitumor, and antihypertensive effects, bearing a huge market demand. Currently, the mainstream industrial approach for steroid drugs production is microbial semi-synthesis, which involves microbial degradation of phytosterols into steroid-drug intermediates (precursors) followed by chemical modification. This review focuses on Mycobacterium sp., a representative strain used for synthesizing steroid-drug intermediates, and outlines the key steps in its steroid metabolic pathway, including sterol uptake, initial oxidation of sterol nucleus, side chain degradation, further oxidation of sterol nucleus, and nucleus cleavage, along with the key enzymes involved. Furthermore, the genetic modification systems of gene overexpression, knockout and knockdown applicable to Mycobacterium are summarized. However, the identification and characterization of complex enzyme systems in the degradation process of sterol side chain remains a major challenge in current research and a key bottleneck restricting the development of novel steroid-drug intermediates. Therefore, accelerating the analysis of sterol metabolic pathways by high-throughput sequencing, bioinformatics analysis and site-directed saturation mutagenesis is essential for the rational design of mycobacterial cell factories and for the construction of strains with high-yield of new steroid intermediates.
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| 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 |
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