Bioresources and Bioprocessing ( IF 4.3 ) Pub Date : 2022-11-04 , DOI: 10.1186/s40643-022-00602-7 Daria N Tekucheva 1 , Vera M Nikolayeva 1 , Mikhail V Karpov 1 , Tatiana A Timakova 1 , Andrey V Shutov 1 , Marina V Donova 1
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The main male hormone, testosterone is obtained from cheap and readily available phytosterol using the strains of Mycolicibacterium neoaurum VKM Ac-1815D, or Ac-1816D. During the first “oxidative” stage, phytosterol (5–10 g/L) was aerobically converted by Ac-1815D, or Ac-1816D to form 17-ketoandrostanes: androstenedione, or androstadienedione, respectively. At the same bioreactor, the 17-ketoandrostanes were further transformed to testosterone due to the presence of 17β-hydroxysteroid dehydrogenase activity in the strains (“reductive” mode). The conditions favorable for “oxidative” and “reductive” stages have been revealed to increase the final testosterone yield. Glucose supplement and microaerophilic conditions during the “reductive” mode ensured increased testosterone production by mycolicibacteria cells. Both strains effectively produced testosterone from phytosterol, but highest ever reported testosterone yield was achieved using M. neoaurum VKM Ac-1815D: 4.59 g/l testosterone was reached from 10 g/l phytosterol thus corresponding to the molar yield of over 66%. The results contribute to the knowledge on phytosterol bioconversion by mycolicibacteria, and are of significance for one-pot testosterone bioproduction from phytosterol bypassing the intermediate isolation of the 17-ketoandrostanes.
Graphical Abstract
中文翻译：
新金分枝杆菌菌株从植物甾醇生物生产睾酮：“一锅法”，两种模式
主要的雄性激素睾酮是使用新金分枝杆菌VKM Ac-1815D 或 Ac-1816D 菌株从廉价且容易获得的植物甾醇中获得的。在第一个“氧化”阶段，植物甾醇 (5–10 g/L) 被 Ac-1815D 或 Ac-1816D 有氧转化，分别形成 17-酮雄甾烷：雄烯二酮或雄甾二烯二酮。在同一生物反应器中，由于菌株中存在 17β-羟基类固醇脱氢酶活性（“还原”模式），17-酮雄甾烷进一步转化为睾酮。研究表明，有利于“氧化”和“还原”阶段的条件可以提高最终睾酮产量。 “还原”模式期间的葡萄糖补充和微需氧条件确保了分枝杆菌细胞产生睾酮的增加。两种菌株均有效地从植物甾醇产生睾酮，但使用M. neoaurum VKM Ac-1815D 实现了有史以来报道的最高睾酮产量：从 10 g/l 植物甾醇达到 4.59 g/l 睾酮，因此对应于超过 66% 的摩尔产率。该结果有助于分枝杆菌生物转化植物甾醇的认识，并且对于绕过17-酮雄甾烷中间分离从植物甾醇一锅法生物生产睾酮具有重要意义。
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