Studies onGeobacillus stearothermophilus-Part V1: Transformation of 17α-hydroxyprogesterone and 21-hydroxyprogesterone

Abstract

Side chain cleavage by biotransformation of 17a-hydroxyprogesterone 1 and 21-hydroxyprogesterone 2 by the thermophile, Geobacillus stearothermophilus was investigated. The side chain cleavage product, androst-4-ene-3,17-dione 1a & 2a, was a common product formed from both substrates. 17a-hydroxy-5a-pregnane-3,6,20-trione 1b and 17a-20a-dihydroxyprogesterone 1c were formed from 1. A rare 17-carboxylic acid analogue of androstene 2b, a transformation product of 2, was also identified. G. stearothermophilus also facilitated hydroxylation of 17a-hydroxyprogesterone at 6a-and 6b-positions resulting in 6b,17a-dihydroxyprogesterone 1d, 6a,17a-dihydroxyprogesterone 1e, 6b,21-dihydroxyprogesterone 2c and 6a,21-dihydroxyprogesterone 2d. All transformation products were identified through their spectral data and comparison with reference compounds.

Predominant allylic hydroxylation at carbons 6 and 7 of 4 and 5-ene functionalized steroids by the thermophilic fungus Rhizomucor tauricus IMI23312

“…[13]. (6) 1730,1700, 1696, 1676 1652 6␤-Hydroxy-androst-4-en-3,17-dione (7) 1730, 1664 1611 3446 6␤,11␣-Dihydroxy-androst-4-en-3,17-dione (8) 1734, 1663 br 1648 3381 br 6␣-Hydroxy-androst-4-en-3,17-dione (9) 1732, 1654 1610 3499 7␣-Hydroxy-androst-4-en-3,17-dione (10) 1736, 1656 1612 3419 6␤-Hydroxytestosterone (11) 1730 1654 3367 12␤-Hydroxytestosterone (12) 1734 1657 3369 br 3␤,7␤,12␤-Trihydroxypregn-5-en-20-one (15) 1695 1653 3398 br 3␤,7␣-Dihydroxy-androst-5en-17-one (16) 1736 1622 3347, 3159 3␤,7␤-Dihydroxy-androst-5en-17-one (17) 1739 1666 3236 br Table 6 Product yields following chromatography In comparison to the 1 H NMR spectrum of (2) 6␤-hydroxy-androst-4-en-3,17-dione (9), isolated as a gum, demonstrated a significant downfield shift (0.2 ppm) for the 19-methyl group protons. A new signal was present at 4.39 ppm (t) indicating monohydroxylation which, was confirmed by accurate mass measurement (HRMS ESI: M + Na + calc.…”

“…Furthermore ␤-carbon downfield shifts were observed for C-6 (9.62 ppm) and C-8 (5.08 ppm) with a ␥-carbon upfield shift for C-14 (4.26 ppm). Compound (8) crystallized as needles from petroleum ether in ethyl acetate m.p. 236 • C and were consistent with literature values, 230-234 • C [18].…”

“…These distinctive properties have resulted in significant application of thermostable enzymes in both the sugar and paper industries [4]. To date of all the species of thermophiles only thermophilic Bacilli have been applied to steroid transformation and have achieved a range of oxidative reactions and generation of novel metabolites [5][6][7][8]. The application of thermophilic fungi to steroid transformation has not been investigated and represents a potentially rich source for the generation of new steroidal compounds and determination of metabolic information [9,10].…”

Transformation of chenodeoxycholic acid by thermophilic Geobacillus stearothermophilus

“…In our earlier studies, we applied thermophilic Geobacillus stearothermophilus for the transformation of steroids, amino acids, and aromatic compounds [15], [18], [19]. In this study, we report transformation of chenodeoxycholic acid (CDCA) by thermophilic G. stearothermophilus.…”

Полногеномное секвенирование термофильного штамма Saccharopolyspora hirsuta subsp. hirsuta ВКМ Ac-666T, перспективного для биотехнологии стероидов

“…Однако сообщения об использовании термофильных бактерий, способных специфически модифицировать стероидные соединения, крайне редки (3). Сообщалось о способности лишь некоторых термофильных микроорганизмов модифицировать стероиды (4)(5)(6)(7)(8)(9). Умеренно термофильный актинобактериальный штамм Saccharopolyspora hirsuta subsp.…”