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.

• PMID: 28281527
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Gajewski J, Pavlovic R, Fischer M, Boles E, Grininger M

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