title: Engineering fungal de novo fatty acid synthesis for short chain fatty acid production.
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-1in 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.
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Gajewski
authors.affiliation: Institute of Molecular Biosciences, Department of Biological Sciences, Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
authors.forename: Renata
authors.initials: R
authors.lastname: Pavlovic
authors.affiliation: 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.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Institute of Molecular Biosciences, Department of Biological Sciences, Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Boles
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Grininger
mesh_terms: D002208:Caproates / Q000378:metabolism; D002210:Caprylates / Q000378:metabolism; D020134:Catalytic Domain; D064429:Fatty Acid Synthases / Q000235:genetics* / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000096:biosynthesis*; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007218:Industrial Microbiology; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D015202:Protein Engineering / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002208:Caproates; D002210:Caprylates; D005232:Fatty Acids, Volatile; D029701:Saccharomyces cerevisiae Proteins; C037652:hexanoic acid; D064429:Fatty Acid Synthases; C031492:octanoic acid