G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Pushchino, Russia.
Methods Mol Biol. 2023;2704:3-21. doi: 10.1007/978-1-0716-3385-4_1.
The microbiological transformation of sterols is currently the technological basis for the industrial production of valuable steroid precursors, the so-called synthons, from which a wide range of steroid and indane isoprenoids are obtained by combined chemical and enzymatic routes. These compounds include value-added corticoids, neurosteroids, sex hormones, bile acids, and other terpenoid lipids required by the medicine, pharmaceutical, food, veterinary, and agricultural industries.Progress in understanding the molecular mechanisms of microbial degradation of steroids, and the development and implementation of genetic technologies, opened a new era in steroid biotechnology. Metabolic engineering of microbial producers makes it possible not only to improve the biocatalytic properties of industrial strains by enhancing their target activity and/or suppressing undesirable activities in order to avoid the formation of by-products or degradation of the steroid core, but also to redirect metabolic fluxes in cells towards accumulation of new metabolites that may be useful for practical applications. Along with whole-cell catalysis, the interest of researchers is growing in enzymatic methods that make it possible to carry out selective structural modifications of steroids, such as the introduction of double bonds, the oxidation of steroidal alcohols, or the reduction of steroid carbonyl groups. A promising area of research is strain engineering based on the heterologous expression of foreign steroidogenesis systems (bacterial, fungal, or mammalian) that ensure selective formation of demanded hydroxylated steroids.Here, current trends and progress in microbial steroid biotechnology over the past few years are briefly reviewed, with a particular focus on the application of metabolic engineering and synthetic biology techniques to improve existing and create new whole-cell microbial biocatalysts.
甾醇的微生物转化目前是从有价值的甾体前体，即所谓的“合成子”，通过化学和酶法联合路线生产各种甾体和茚满异戊二烯的工业生产的技术基础。这些化合物包括有附加值的皮质激素、神经甾体、性激素、胆酸和医药、制药、食品、兽医和农业行业所需的其他萜类脂质。
对微生物降解甾体的分子机制的理解的进展，以及遗传技术的开发和实施，开创了甾体生物技术的新时代。微生物生产者的代谢工程不仅使通过增强其目标活性和/或抑制甾体核心降解或副产物形成来改善工业菌株的生物催化特性成为可能，而且还使细胞中的代谢通量重新定向到新代谢物的积累，这些代谢物可能对实际应用有用。除了全细胞催化外，研究人员对能够进行甾体选择性结构修饰的酶法越来越感兴趣，例如引入双键、甾醇醇的氧化或甾体羰基的还原。基于异源表达外源甾体生物合成系统（细菌、真菌或哺乳动物）的菌株工程是一个很有前途的研究领域，该系统可确保有需求的羟基化甾体的选择性形成。
本文简要综述了过去几年中微生物甾体生物技术的最新趋势和进展，特别关注代谢工程和合成生物学技术在改进现有和创造新型全细胞微生物生物催化剂中的应用。
