Microbial Biotransformation of Steroidal Compounds

Microbial biotransformation of steroidal compounds harnesses the catalytic repertoire of bacteria and fungi to modify complex sterol structures, offering regio- and stereospecific transformations that are difficult to achieve by purely chemical means. Key microbial hosts, particularly actinobacteria such as Mycobacterium and Rhodococcus species, convert abundant feedstocks like phytosterols and cholesterol into high-value steroid synthons, including androst-4-ene-3,17-dione and 9α-hydroxy compounds. These intermediates serve as precursors for sex hormones, corticosteroids and anabolic agents in the pharmaceutical industry. Advances in genomics and comparative bioinformatics have mapped the distribution of aerobic 9,10-seco pathways across environmental isolates, while enzyme engineering and synthetic biology approaches have begun to tailor monooxygenases, dehydrogenases and CoA-ligases for improved activity, selectivity and robustness. Recent efforts in cell-wall engineering, cofactor balancing and pathway modularisation have yielded microbial cell factories with enhanced uptake of hydrophobic substrates and elevated productivities. Beyond industrial biocatalysis, environmental studies reveal that microbial steroid degradation contributes to carbon cycling in soil, aquatic and host-associated microbiomes, underscoring its global ecological significance.

Research from Nature Portfolio

Recent studies have dissected the dual‐function 17β-hydroxysteroid dehydrogenase/β-hydroxyacyl-CoA dehydrogenase (Hsd4A) in Mycobacterium neoaurum, revealing its pivotal role in sterol side-chain degradation. Deletion and overexpression experiments defined two competing pathways that channel substrates into the production of 23,24-bisnorcholenic steroids. Metabolic engineering of hsd4A alongside complementary genes produced strains with significantly improved titres and rates of bisnorcholenic steroid formation. These findings establish a mechanistic framework for precision biocatalysis of sterol feedstocks into tailored synthons for downstream chemical elaboration.

Microbial Biotransformation of Steroidal Compounds publication trend

The graph below shows the total number of articles in microbial biotransformation of steroidal compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Biotransformation: Microbial-catalysed chemical modification of a compound, often yielding regio- and stereospecific products.

Phytosterols: Plant-derived sterols structurally similar to cholesterol, used as feedstocks for microbial steroid conversion.

Steroid synthons: Core intermediates bearing modified steroid skeletons that serve as building blocks for pharmaceutical steroids.

Monooxygenase: Enzyme class that incorporates one atom of molecular oxygen into substrates, critical for steroid hydroxylation.

CoA thioester: Intermediate in catabolic pathways in which a substrate is activated by conjugation to coenzyme A for further enzymatic processing.

References

1. New Insights on Steroid Biotechnology. Frontiers in Microbiology (2018).
2. Unraveling and engineering the production of 23,24-bisnorcholenic steroids in sterol metabolism. Scientific Reports (2016).
3. Delineation of Steroid-Degrading Microorganisms through Comparative Genomic Analysis. mBio (2016).
4. Metagenomes Reveal Global Distribution of Bacterial Steroid Catabolism in Natural, Engineered, and Host Environments. mBio (2018).
5. Cofactor engineering to regulate NAD+/NADH ratio with its application to phytosterols biotransformation. Microbial Cell Factories (2017).
6. Enhancing the bioconversion of phytosterols to steroidal intermediates by the deficiency of kasB in the cell wall synthesis of Mycobacterium neoaurum. Microbial Cell Factories (2020).