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

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

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Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence 'Macromolecular Complexes', Goethe University Frankfurt, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany.
Institute of Molecular Biosciences, Department of Biological Sciences, Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.


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.

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