Predominant allylic hydroxylation at carbons 6 and 7 of 4 and 5-ene functionalized steroids by the thermophilic fungus Rhizomucor tauricus IMI23312.
This paper demonstrates for the first time transformation of a series of steroids (progesterone, androst-4-en-3,17-dione, testosterone, pregnenolone and dehydroepiandrosterone) by the thermophilic fungus Rhizomucor tauricus. All transformations were found to be oxidative (monohydroxylation and dihydroxylation) with allylic hydroxylation the predominant route of attack functionalizing the steroidal skeleta. Timed experiments demonstrated that dihydroxylation of progesterone, androst-4-en-3,17-dione and pregnenolone all initiated with hydroxylation on ring-B followed by attack on ring-C. Similar patterns of steroidal transformation to those observed with R. tauricus have been observed with some species of thermophilic Bacilli and mesophilic fungi. All metabolites were isolated by column chromatography and were identified by (1)H, (13)C NMR, DEPT analysis and other spectroscopic data. The application of thermophilic fungi to steroid transformation may represent a potentially rich source for the generation of new steroidal compounds as well as for uncovering inter and intraspecies similarities and differences in steroid metabolism.
Hunter
A Christy
AC
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy, University of Brighton, Lewes Road, Brighton, East Sussex, UK. c.hunter@bton.ac.uk
Mills
Paul W
PW
Dedi
Cinzia
C
Dodd
Howard T
HT
D002244:Carbon / Q000378:metabolism*; D006900:Hydroxylation; D008954:Models, Biological; D008958:Models, Molecular; D020103:Rhizomucor / Q000201:enzymology* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature
D013256:Steroids; D002244:Carbon; D013250:Steroid Hydroxylases