The Missing Piece in Biosynthesis of Amphidinols: First Evidence of Glycolate as a Starter Unit in New Polyketides from Amphidinium carterae

Mar Drugs. 2017 May 31;15(6):157. doi: 10.3390/md15060157.

Abstract

Two new members of the amphidinol family, amphidinol A (1) and its 7-sulfate derivative amphidinol B (2), were isolated from a strain of Amphidinium carterae of Lake Fusaro, near Naples (Italy), and chemically identified by spectroscopic and spectrometric methods. Amphidinol A showed antifungal activity against Candida albicans (MIC = 19 µg/mL). Biosynthetic experiments with stable isotope-labelled acetate allowed defining the elongation process in 1. For the first time the use of glycolate as a starter unit in the polyketide biosynthesis of amphidinol metabolites was unambiguously demonstrated.

Keywords: Amphidinium; Candida albicans; PKS; SHAM; amphidinol; amphidinol-related polyketide; antifungal polyketide; dinoflagellate, glycolate; polyketide biosynthesis.

MeSH terms

  • Alkenes / metabolism*
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects
  • Dinoflagellida / metabolism*
  • Glycolates / metabolism*
  • Polyketides / metabolism*
  • Polyketides / pharmacology
  • Pyrans / metabolism*

Substances

  • Alkenes
  • Antifungal Agents
  • Glycolates
  • Polyketides
  • Pyrans
  • amphidinol 2