Bioconversion of 6-(N-methyl-N-phenyl)aminomethyl androstane steroids by Nocardioides simplex

• Published in: Steroids Vol. 118; pp. 9 - 16
• Main Authors: Sukhodolskaya, Galina, Fokina, Victoria, Shutov, Andrei, Nikolayeva, Vera, Savinova, Tatiana, Grishin, Yuri, Kazantsev, Alexey, Lukashev, Nikolay, Donova, Marina
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 01.02.2017; Elsevier
• Subjects: 3-Ketosteroid Δ1-dehydrogenase; 6(α/β)-(N-methyl-N-phenyl)aminomethyl androstanes; Actinobacteria; Actinobacteria - metabolism; Androstanes - chemistry; Androstanes - metabolism; Biochemistry & Molecular Biology; Biotransformation; Endocrinology & Metabolism; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Molecular Structure; Nocardioides simplex; Science & Technology; Stereoisomerism; Steroids - chemistry; Steroids - metabolism; Nocardioides simplex; ADD; KSHB; 6(α/β)-(N-methyl-N-phenyl)aminomethyl-AD; KSHA; DMSO; Androsta-1,4-diene-3,17-dione (PubChem CID: 13472); 6(α/β)-(N-methyl-N-phenyl)aminomethyl-ADD; 17β-HSD; MTBE; TFA; DT; T; Biotransformation; 6(α/β)-(N-methyl-N-phenyl)aminomethyl-DT; Actinobacteria; Androst-4-ene-3,17-dione (PubChem CID: 6128); Dehydrotestosterone (PubChem CID: 6422); Testosterone (PubChem CID: 6013); 6(α/β)-(N-methyl-N-phenyl)aminomethyl androstanes; AD; 6(α/β)-(N-methyl-N-phenyl)aminomethyl-T; 3-Ketosteroid Δ1-dehydrogenase; 9α-OH-AD; 9α-KSH; KSTD; 3-Ketosteroid Delta-dehydrogenase; 3-KETOSTEROID 9-ALPHA-HYDROXYLASE; RHODOCOCCUS-ERYTHROPOLIS SQ1; 3-KETOSTEROID-DELTA-DEHYDROGENASE; ENZYMES; MICROBIAL CONVERSION; DEGRADATION; Biotransformation 6(alpha/beta)-(N-methyl-N-phenyl)aminomethyl androstanes; 3-KETOSTEROID-9-ALPHA-HYDROXYLASE; 3-Ketosteroid Δ-dehydrogenase
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2016.11.001

[Display omitted] •Nocardioides simplex converts 6-(N-methyl-N-phenyl)aminomethyl androstanes.•Only β-stereoisomers undergo 1(2)-dehydrogenation with N. simplex cells.•(N-methyl-N-phenyl)aminomethyl substitution at C6 prevents biodegradation of steroid core. The newly synthesized (α/β)-diastereomers of 6-(N-methyl-N-phenyl)aminomethylandrost-4-ene-3,17-dione (5) and 6-(N-methyl-N-phenyl)aminomethylandrost-4-en-17β-ol-3-one (6) were firstly investigated as substrates for the whole cells of Nocardioides simplex VKM Ac-2033D in comparison with their unsubstituted analogs, – androst-4-ene-3,17-dione (1) and androst-4-en-17β-ol-3-one (2). 1(2)-Dehydroderivatives were identified as the major bioconversion products from all the substrates tested. When using the mixtures of (α/β)-stereoisomers of 5 and 6 as the substrates, only β-stereoisomers of the corresponding 1,4-diene-steroids were formed. Along with 1(2)-dehydrogenation, N. simplex VKM Ac-2033D promoted oxidation of the hydroxyl group at C-17 position of 6: both 6(α) and 6(β) were transformed to the corresponding 17-keto derivatives. No steroid core destruction was observed during the conversion of the 6-substituted androstanes 5 and 6, while it was significant when 1 or 2 was used as the substrate. The results suggested high potentials of N. simplex VKM Ac-2033D for the generation of novel 1(2)-dehydroanalogs.