Flexibility of the endogenous progesterone lactonisation pathway in Aspergillus tamarii KITA: transformation of a series of cortical steroid analogues

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

“…Similar fungal metabolic handling of the tested substrates has been observed in a wide range of non-thermophilic fungi with 4-ene [22][23][24] and 5-ene containing steroids [20,21,23,[25][26][27][28][29]. Interestingly, allylic oxidation of progesterone (1) at C-6 has been observed in two species of thermophilic Bacilli [5,30], however, side-chain degradation and reductive transformation observed in both thermophilic Bacilli and non-thermophilic fungi [5,31,32] were not detected.…”

Transformation of a series of saturated isomeric steroidal diols by Aspergillus tamarii KITA reveals a precise stereochemical requirement for entrance into the lactonization pathway

“…3␣-Hydroxy-17a-oxa-D-homo-5␣-androstan-17-one (21) was identified by comparison of its' spectra to that of (7) this demonstrated a significant downfield shift for the 18-methyl protons of 0.44-1.30 ppm which is fully indicative of hetero-atom insertion [2,3,6] in ring-D. This was supported in the 13 C NMR spectrum with downfield shifts for C-13 (35.96 ppm) and C-18 (8.96 ppm), directly associated with insertion of the hetero-atom, and upfield shifts consistent with the reduced 6 membered ring strain for C-14 (8.08 ppm) and C-17 (48.60 ppm).…”

“…1) which converts progesterone (1) via Baeyer-Villiger oxidation to testosterone acetate (2). This undergoes hydrolysis to form testosterone (3) and is then oxidised to androst-4-en-3,17-dione (4).…”

“…Divergence from this pathway can occur through testosterone (3) which, can be functionalized by a hydroxylase affording 11␤-hydroxytestosterone. Progesterone (1) can also undergo reversible reduction of the C-20 ketone resulting in (6), the equilibrium between the reductase and the oxidase is thought to be dynamic [2]. 20(R)-Reduction products of progesterone analogues have been isolated in a number of studies [2,3].…”

“…Steroids differing in side-chain structure [2,3] substituent position [4,5] and ring-D structure [6,7] have been transformed in whole cell cultures of A. tamarii. These studies have demonstrated that a wide-range of structurally diverse steroids can be handled by the endogenous pathways within this organism, and have highlighted the powerful effect of single functional groups in directing their metabolic fate (oxidative or reductive) [3,6,7].…”