Stereoselective 15α-hydroxylation of androsta-1,4-diene-3,17-dione by Gibberella sp. for efficient production of 15α-OH-ADD and 15α-OH-AD

TL;DR

Researchers used Gibberella sp. to efficiently produce important steroid drug intermediates through selective hydroxylation.

Contribution

Gibberella sp. was optimized for high-yield stereoselective hydroxylation of ADD into pharmaceutical intermediates.

Findings

Gibberella sp. selectively produced 15α-OH-ADD and 15α-OH-AD from ADD with high efficiency.

Optimized conditions increased the transformation rate of ADD to 15α-OH-ADD from 30.35% to 61.74%.

Methanol as a cosolvent improved biotransformation efficiency in Gibberella sp.

Abstract

Androsta-1,4-diene-3,17-dione (ADD) and its hydroxylated derivatives are important steroidal drug intermediates, playing a crucial role in the pharmaceutical industry. This study evaluated the whole-cell biotransformation of ADD by Gibberella sp. CICC 2498 and Absidia sp. CICC 41050. While Absidia sp. showed low efficiency, Gibberella sp. selectively produced two major metabolites, identified as 15α-OH-ADD and 15α-OH-AD via HPLC, MS, and NMR. Through orthogonal design and single-factor experiments, the transformation rate of ADD to 15α-OH-ADD was enhanced from 30.35% to 61.74% under optimal conditions: 1 g L−1 ADD, 12% inoculum, 70 mL medium volume, 120 h incubation, and 1% (v/v) methanol as cosolvent. These results highlight Gibberella sp. as a promising biocatalyst for regio- and stereoselective steroid hydroxylation, providing an efficient microbial strategy for high-value steroidal intermediates in pharmaceutical manufacturing.

Biocatalytic hydroxylation of steroids by Gibberella sp. in steroid intermediate synthesis. Products identification and biotransformation optimization. Efficient 15α-OH-ADD production and industrial potential by Gibberella sp.

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