Improving the production of 9α-hydroxy-4-androstene-3,17-dione from phytosterols by 3-ketosteroid-Δ¹-dehydrogenase deletions and multiple genetic modifications in Mycobacterium fortuitum.

ABSTRACT:

Background

9α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) is a significant intermediate for the synthesis of glucocorticoid drugs. However, in the process of phytosterol biotransformation to manufacture 9-OHAD, product degradation, and by-products restrict 9-OHAD output. In this study, to construct a stable and high-yield 9-OHAD producer, we investigated a combined strategy of blocking Δ¹‑dehydrogenation and regulating metabolic flux.

Results

Five 3-Ketosteroid-Δ¹-dehydrogenases (KstD) were identified in Mycobacterium fortuitum ATCC 35855. KstD2 showed the highest catalytic activity on 3-ketosteroids, followed by KstD3, KstD1, KstD4, and KstD5, respectively. In particular, KstD2 had a much higher catalytic activity for C9 hydroxylated steroids than for C9

SUBMITTER: Liu X 

PROVIDER: S-EPMC10018825 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature