Engineering fungal de novo fatty acid synthesis for short chain fatty acid production

Nat Commun. 2017 Mar 10:8:14650. doi: 10.1038/ncomms14650.

Abstract

Fatty acids (FAs) are considered strategically important platform compounds that can be accessed by sustainable microbial approaches. Here we report the reprogramming of chain-length control of Saccharomyces cerevisiae fatty acid synthase (FAS). Aiming for short-chain FAs (SCFAs) producing baker's yeast, we perform a highly rational and minimally invasive protein engineering approach that leaves the molecular mechanisms of FASs unchanged. Finally, we identify five mutations that can turn baker's yeast into a SCFA producing system. Without any further pathway engineering, we achieve yields in extracellular concentrations of SCFAs, mainly hexanoic acid (C6-FA) and octanoic acid (C8-FA), of 464 mg l-1 in total. Furthermore, we succeed in the specific production of C6- or C8-FA in extracellular concentrations of 72 and 245 mg l-1, respectively. The presented technology is applicable far beyond baker's yeast, and can be plugged into essentially all currently available FA overproducing microorganisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caproates / metabolism
  • Caprylates / metabolism
  • Catalytic Domain
  • Fatty Acid Synthases / genetics*
  • Fatty Acid Synthases / metabolism
  • Fatty Acids, Volatile / biosynthesis*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Industrial Microbiology
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation
  • Protein Engineering / methods*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Caproates
  • Caprylates
  • Fatty Acids, Volatile
  • Saccharomyces cerevisiae Proteins
  • hexanoic acid
  • Fatty Acid Synthases
  • octanoic acid