Metabolism of steroidal lactones by the fungus Corynespora cassiicola CBS 161.60 results in a mechanistically unique intramolecular ring-D cyclization resulting in C-14 spiro-lactones

Research output: Contribution to journalArticle

  • External authors:
  • A. Christy Hunter
  • Yewande Inatimi Oni
  • Howard T Dodd
  • James Raftery
  • Megan Uttley

Abstract

The fungus Corynespora cassiicola metabolises exogenous steroids in a unique and highly specific manner. Central to this, is the ability of this organism to functionalise substrates (androgens, progestogens) at the highly stereochemically hindered 8β-position of the steroid nucleus. A recent study has identified that 8β-hydroxylation occurs through inverted binding in a 9α-hydroxylase. In order to discern the metabolic fate of more symmetrical molecules, we have investigated the metabolism of a range of steroidal analogues functionalised with ring-D lactones, but differing in their functional group stereochemistry at carbon-3. Remarkably, the 3α-functionalised steroidal lactones underwent a mechanistically unique two step intramolecular cyclisation resulting in the generation of a ring-D spiro-carbolactone. This rapid rearrangement initiated with hydroxylation at carbon 14 followed by transesterification, resulting in ring contraction with formation of a butyrolactone at carbon-14. Remarkably this rearrangement was found to be highly dependent on the stereochemistry at carbon-3, with the β-analogues only undergoing 9α-hydroxylation. The implications of these findings and their mechanistic bases are discussed.

Bibliographical metadata

Original languageEnglish
Pages (from-to)939-945
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1862
Issue number9
Early online date9 Jun 2017
DOIs
Publication statusPublished - Sep 2017

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