分枝杆菌转化植物甾醇定向积累甾药 中间体的代谢工程研究进展Advance in metabolic engineering for bioconversion of phytosterols into steroid metabolites by Mycobacterium sp.

Abstract

甾体激素类药物在医药工业中地位突出，是仅次于抗生素的第二大类化学药物。甾体激素类药物的合成往往依赖于AD、ADD、9α-OH-AD、4-BNA等关键中间体的高质量生产，工业微生物转化植物甾醇发酵生产甾药中间体已成为当今甾体药物工业发展的主流。综述了工业分枝杆菌转化植物甾醇的代谢途径、关键酶系和分子机制，归纳了近年来利用基因工程技术对分枝杆菌植物甾醇代谢途径进行改造以定向积累目标甾药中间体的研究进展，并对未来的研究方向进行了预测，以期为甾药中间体的绿色生物制造提供有价值的参考。Steroid hormone drug is an important category in the pharmaceutical industry, and is the second largest drug after antibiotic. The synthesis of almost all steroid hormone drug starts from the quality production of steroid metabolites such as AD, ADD, 9α-OH-AD and 4-BNA. Bioconversion of phytosterols into steroid metabolites has become the mainstream of industrial production of steroid drugs. The metabolic pathway, key enzymes and molecular mechanism involved in phytosterols degradation by Mycobacterium sp. were reviewed, and the research progress on using genetic engineering technology to modify the phytosterol metabolic pathway of Mycobacterium sp. to accumulate target steroid metabolites in recent years were summarized. The future research direction was predicted in order to provide a valuable reference for the green biological manufacture of steroid metabolites.

Keywords

• 分枝杆菌；植物甾醇；生物转化；甾药中间体；代谢途径；代谢工程
• mycobacterium sp.; phytosterols; bioconversion; steroid metabolites; metabolic pathway; metabolic engineering