Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14650
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Funding
- Hessian Ministry of Science and Art via the LOEWE research focus 'Integrative fungal research (IPF)'
- Volkswagen Foundation [85701]
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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 (C-6-FA) and octanoic acid (C-8-FA), of 464 mg l(-1) in total. Furthermore, we succeed in the specific production of C-6- or C-8-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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