Preparation of androsta-1,4-diene-3,17-dione from sterols using Mycobacterium neoaurum VKPM Ac-1656 strain

Abstract

A product of microbiological cleavage of the sterols side chain, androsta-1,4-diene-3,17-dione, is toxic for bacteria, in particular, actinobacteria of the genera Mycobacterium and Arthrobacter. Sterols were transformed into androsta-1,4-diene-3,17-dione by culturing the M. neoaurum VKPM An-1656 strain in a high yield, provided that a sorbent was used for elimination of contact between the bacterial cells and the product. Unlike the cholesterol side chain, the more branched chains of phytosterols were cleaved in the presence of M. neoaurum at a high rate only under turbulent stirring of the culture medium, which intensified the formation of hydrocarbonate ion from NaNI3 in situ.

Inactivation and Augmentation of the Primary 3-Ketosteroid-Δ 1 - Dehydrogenase in Mycobacterium neoaurum NwIB-01: Biotransformation of Soybean Phytosterols to 4-Androstene- 3,17-Dione or 1,4-Androstadiene-3,17-Dione

“…To improve biotransformation, bacteria have been subjected to mutagenesis by UV/chemical treatments (10,17,18,19,21) and metabolic engineering (23,24,25,27). However, most of the resulting strains produce AD and ADD simultaneously, which impedes their utility (11,13).…”

From Soybean Phytosterols to Steroid Hormones

“…Most phytosterol-transforming strains can transform phytosterols into many structurally similar products, such as the C19 steroids AD, ADD, and their derivatives, at the same time (Egorova, et al, 2002;Donova, et al, 2005aDonova, et al, , 2005bDonova, et al, , 2005cMolchanova, et al, 2007). Because the differences in the structures of these products are very subtle, it is difficult to separate and purify them.…”

“…Because the differences in the structures of these products are very subtle, it is difficult to separate and purify them. This significantly complicates the production process and increases production costs (Molchanova, et al, 2007). An ideal microbial strain, therefore, must be able to transform phytosterols into only a single desired product.…”

“…Although several methods of sequestering toxic steroids from the reaction media have been tested, the development of mutants with improved tolerance to steroid products may be a more effective way to bypass the toxic effects of steroid products on microbial cells (Molchanova, et al, 2007;Perez, et al, 2003;Malaviya & Gomes, 2008). An ideal organism should have physiological functions that reduce or eliminate the harmful effects of toxic products.…”

Fractionation of free and conjugated steroids for the detection of boldenone metabolites in calf urine with ultra‐performance liquid chromatography/tandem mass spectrometry

“…In the pharmaceutical sector phytosterols are often used as a precursor for microbial transformation to androsta-1,4-diene-3,17-dione (ADD; Fig. 1), 7,8 a key compound in the synthesis of pharmacologically active steroids and precursors of b-boldenone. 9 An experiment in 2000 proved that the feeding of phytosterols to rats led to the detection of ADD and androst-4-ene-3,17-dione (AED; Fig.…”