Ring-B functionalized androst-4-en-3-ones and ring-C substituted pregn-4-en-3-ones undergo differential transfonnation in Aspergillus tamarii KITA: Ring-A transformation with all C-6 substituted steroids and ring-D transfonnation with C-11 substituents

A.C. Hunter, Jacqueline Elsom, L. Ross, R. Barrett

Research output: Contribution to journalArticle

Abstract

The fungus Aspergillus tamarii transforms progesterone 1 into testololactone 5 in high yield through a four-step enzymatic pathway which is flexible to a range of steroidal substrates. To date, no studies have investigated the fate of C-6 (ring-B) and C-11 (ring-C) functionalized steroidal substrates on metabolism. Remarkably all of the C-6 functionalized substrates underwent reductive metabolism on ring-A in contrast to C-11 functionalized steroids where only ring-D oxidative or reductive transformation occurred. In order to discern the precise role of the functional groups in directing metabolism 6-ketoprogesterone 10 with functionality at C-6 and the ring-D methyl ketone underwent reductive and oxidative transformation on both terminal A and D rings showing that this functionality was directing metabolism. Androst-4-en-3,6-dione 12 devoid of ring-D functionality underwent reductive metabolism on ring-A proving that the C-6 functionality was directing metabolism to this ring with the ring-D methyl ketone responsible for generating transformation at this position. Functionality at C-11 exclusively controlled entry into and degree of metabolism on the lactonization pathway. These novel findings may have important bearing in the future understanding of structure activity relationships in revealing new metabolic pathways and further affords a unique opportunity for generation of novel bioactive steroidal compounds.
Original languageEnglish
Pages (from-to)360-366
Number of pages7
JournalBiochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids
Volume1761
Issue number3
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Steroid transformation
  • Aspergillus tamarii
  • Baeyer–Villiger oxidation
  • Androst-4-en-3-one
  • Pregn-4-en-3-one

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