Investigation of a 6-MSA Synthase Gene Cluster in Aspergillus aculeatus Reveals 6-MSA-derived Aculinic Acid, Aculins A-B and Epi-Aculin A

Chembiochem. 2015 Oct 12;16(15):2200-4. doi: 10.1002/cbic.201500210. Epub 2015 Sep 16.


Aspergillus aculeatus, a filamentous fungus belonging to the Aspergillus clade Nigri, is an industrial workhorse in enzyme production. Recently we reported a number of secondary metabolites from this fungus; however, its genetic potential for the production of secondary metabolites is vast. In this study we identified a 6-methylsalicylic acid (6-MSA) synthase from A. aculeatus, and verified its functionality by episomal expression in A. aculeatus and heterologous expression in A. nidulans. Feeding studies with fully (13) C-labeled 6-MSA revealed that 6-MSA is incorporated into aculinic acid, which further incorporates into three compounds that we name aculins A and B, and epi-aculin A, described here for the first time. Based on NMR data and bioinformatic studies we propose the structures of the compounds as well as a biosynthetic pathway leading to formation of aculins from 6-MSA.

Keywords: Aspergillus; biosynthesis; methylsalicylic acid; natural products; polyketide; terpene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Acetates / metabolism*
  • Acyltransferases / genetics*
  • Acyltransferases / metabolism
  • Aspergillus / enzymology*
  • Aspergillus / genetics*
  • Ligases / genetics*
  • Ligases / metabolism
  • Multienzyme Complexes / genetics*
  • Multienzyme Complexes / metabolism
  • Multigene Family*
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Proline / analogs & derivatives*
  • Proline / chemistry
  • Proline / metabolism
  • Pyrones / chemistry
  • Pyrones / metabolism*
  • Salicylates / chemistry
  • Salicylates / metabolism*


  • Acetates
  • Multienzyme Complexes
  • Pyrones
  • Salicylates
  • Proline
  • Oxidoreductases
  • Acyltransferases
  • 6-methylsalicylic acid synthetase
  • Ligases
  • 6-methylsalicylic acid