选择性微生物转化 DHEA 为 7α-OH-DHEA。

Selective Microbial Conversion of DHEA into 7α-OH-DHEA.

机构信息

Federal Research Center "Pushchino Center for Biological Research of the Russian Academy of Sciences", G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Russia.

出版信息

Methods Mol Biol. 2023;2704:269-275. doi: 10.1007/978-1-0716-3385-4_16.

DOI:10.1007/978-1-0716-3385-4_16

PMID:37642850

Abstract

7α-Hydroxy dehydroepiandrosterone (7α-OH-prasterone, 7α-OH-DHEA) is a key steroid intermediate in the synthesis of valuable pharmaceuticals widely used in the treatment of autoimmune illness, rheumatoid arthritis, colitis, and other severe diseases. The steroid can be produced using a filamentous fungus, which is capable of regio- and stereospecific hydroxylation of the steroid 3β-alcohol (DHEA) in the allylic position C7. Here, we describe a method for highly selective microbial production of 7α-OH-DHEA from DHEA using the zygomycete Backusella lamprospora VKM F-944. The method ensures high yield of 7α-OH-DHEA (up to 89%, mol/mol) even at high concentration of the substrate DHEA (15 g/L).

摘要

7α-羟基去氢表雄酮（7α-OH-普拉睾酮，7α-OH-DHEA）是合成有价值药物的关键甾体中间产物，这些药物广泛用于治疗自身免疫性疾病、类风湿性关节炎、结肠炎和其他严重疾病。该甾体可以使用丝状真菌生产，该真菌能够在烯丙位 C7 处对甾体 3β-醇（DHEA）进行区域和立体特异性羟化。在这里，我们描述了使用接合菌 Backusella lamprospora VKM F-944 从 DHEA 中高度选择性地微生物生产 7α-OH-DHEA 的方法。该方法即使在高浓度的底物 DHEA（15 g/L）下，也能保证 7α-OH-DHEA 的高产量（高达 89%，摩尔/摩尔）。