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

  • 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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Author:Jan Gajewski, Renata Pavlovic, Manuel Fischer, Eckhard BolesORCiD, Martin GriningerORCiDGND
URN:urn:nbn:de:hebis:30:3-485581
DOI:https://doi.org/10.1038/ncomms14650
ISSN:2041-1723
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28281527
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/03/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/12/20
Tag:Metabolic engineering; Protein design
Volume:8
Issue:Art. 14650
Page Number:8
First Page:1
Last Page:8
Note:
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/
HeBIS-PPN:446229393
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Biowissenschaften / Biowissenschaften
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0