Engineering fungal nonreducing polyketide synthase by heterologous expression and domain swapping

Org Lett. 2013 Feb 15;15(4):756-9. doi: 10.1021/ol303328t. Epub 2013 Jan 31.

Abstract

We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA in A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) and 6-ethyl-2,4-dihydroxy-3,5-dimethylbenzaldehyde (2). Generation of DtbAΔR+TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehydes / chemistry
  • Aspergillus nidulans / enzymology*
  • Carboxylic Acids / chemistry
  • Molecular Structure
  • Polyketide Synthases / genetics*
  • Polyketide Synthases / metabolism
  • Protein Engineering / methods

Substances

  • Aldehydes
  • Carboxylic Acids
  • Polyketide Synthases