Transformation of 5-ene steroids by the fungus Aspergillus tamarii KITA: Mixed molecular fate in lactonization and hydroxylation pathways with identification of a putative 3β-hydroxy-steroid dehydrogenase/Δ5–Δ4 isomerase pathway

Steroid-transforming enzymes in fungi

“…Recently, 3␤-HSD/isomerase activity was detected in Aspergillus tamarii [119]. This fungus converts 5-ene steroids, such as DHEA and 3␤,17␤-dihydroxyandrost-5-ene, and C-17 side-chain-containing steroids, such as pregnenolone and 3␤-hydroxy-16␣,17␣-epoxypregn-5-en-20-one.…”

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

“…1. The endogenous lactonization pathway present in Aspergillus tamarii KITA, that converts progesterone (1) to testololactone (5) with the preceding C-20 keto-alcohol reducto-oxidase interconverting (1) and (6) and the minor 11␤-hydroxylation pathway from testosterone (3).…”

“…This undergoes hydrolysis to form testosterone (3) and is then oxidised to androst-4-en-3,17-dione (4). A final Baeyer-Villiger oxidation of the C-17 ketone affords testololactone (5) in high yield [1]. Divergence from this pathway can occur through testosterone (3) which, can be functionalized by a hydroxylase affording 11␤-hydroxytestosterone.…”

“…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].…”

Transformation of some 3α-substituted steroids by Aspergillus tamarii KITA reveals stereochemical restriction of steroid binding orientation in the minor hydroxylation pathway

“…The final Baeyer-Villiger oxidation then takes place at the C-17 ketone generating the end product testololactone (5) which does not undergo further metabolism [2]. Within the transformation sequence testosterone (3) can also enter into a minor 11␤-hydroxylation pathway and progesterone (1) can undergo reduction of the C-20 ketone forming the C-20(R)-hydroxy analogue (6). A competitive equilibrium exists between the reductase forming the C-20(R)-alcohol and the oxidase that regenerates (1).…”