TY - JOUR A1 - Gajewski, Jan A1 - Pavlovic, Renata A1 - Fischer, Manuel A1 - Boles, Eckhard A1 - Grininger, Martin T1 - Engineering fungal de novo fatty acid synthesis for short chain fatty acid production T2 - Nature Communications N2 - 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. KW - Metabolic engineering KW - Protein design Y1 - 2017 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48558 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-485581 SN - 2041-1723 N1 - Rights and permissions: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ VL - 8 IS - Art. 14650 SP - 1 EP - 8 PB - Nature Publishing Group UK CY - [London] ER -