An unusual ring--a opening and other reactions in steroid transformation by the thermophilic fungus Myceliophthora thermophila.
A series of steroids (progesterone, testosterone acetate, 17beta-acetoxy-5 alpha-androstan-3-one, testosterone and androst-4-en-3,17-dione) have been incubated with the thermophilic ascomycete Myceliophthora thermophila CBS 117.65. A wide range of biocatalytic activity was observed with modification at all four rings of the steroid nucleus and the C-17beta side-chain. This is the first thermophilic fungus to demonstrate the side-chain cleavage of progesterone. A unique fungal transformation was observed following incubation of the saturated steroid 17beta-acetoxy-5 alpha-androstan-3-one resulting in 4-hydroxy-3,4-seco-pregn-20-one-3-oic acid which was the product generated following the opening of an A-homo steroid, presumably by lactonohydrolase activity. Hydroxylation predominated at axial protons of the steroids containing 3-one-4-ene ring-functionality. This organism also demonstrated reversible acetylation and oxidation of the 17beta-alcohol of testosterone. All steroidal metabolites were isolated by column chromatography and were identified by (1)H, (13)C NMR, DEPT analysis and other spectroscopic data. The range of steroidal modification achieved with this fungus indicates that these organisms may be a rich source of novel steroid biocatalysis which deserve greater investigation in the future.
Hunter
A Christy
AC
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy, University of Brighton, East Sussex BN2 4GJ, UK. c.hunter@bton.ac.uk
Watts
Kieran R
KR
Dedi
Cinzia
C
Dodd
Howard T
HT
D000107:Acetylation; D000731:Androstanes / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D010084:Oxidation-Reduction; D011374:Progesterone / Q000378:metabolism; D020037:Sordariales / Q000201:enzymology*; D013256:Steroids / Q000378:metabolism*; D013739:Testosterone / Q000031:analogs & derivatives
C543728:17-acetoxyandrostan-3-one; D000731:Androstanes; D013256:Steroids; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; C040594:testosterone acetate