Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons

摘要: Summary A number of pharmaceutical steroid synthons are currently produced through the microbial side-chain cleavage natural sterols as an alternative to multi-step chemical synthesis. Industrially, these have been usually fermentative processes using environmental isolated microorganisms or their conventional mutants. Mycobacterium smegmatis mc2155 is a model organism for tuberculosis studies which uses cholesterol sole carbon and energy source growth, other mycobacterial strains. Nevertheless, this property has not exploited industrial production steroidic synthons. Taking advantage our knowledge on degradation pathway M. smegmatis we demonstrated that MSMEG_6039 (kshB1) MSMEG_5941 (kstD1) genes encoding reductase component 3-ketosteroid 9α-hydroxylase (KshAB) ketosteroid Δ1-dehydrogenase (KstD), respectively, indispensable enzymes central metabolism cholesterol. Therefore, constructed gene deletion mutant MS6039 transforms efficiently (e.g. phytosterols) into 1,4-androstadiene-3,17-dione. In addition, double MS6039-5941 [ΔMSMEG_6039 (ΔkshB1) ΔMSMEG_5941 (ΔkstD1)] 4-androstene-3,17-dione with high yields. These findings suggest catabolism in easy handle equally efficient sterol transformation than strains, paving way valuating strain suitable cell factory develop la carte metabolic engineering strategies steroids.