Production of octanoic acid in Saccharomyces cerevisiae: investigation of new precursor supply engineering strategies and intrinsic limitations

  • The eight-carbon fatty acid octanoic acid (OA) is an important platform chemical and precursor of many industrially relevant products. Its microbial biosynthesis is regarded as a promising alternative to current unsustainable production methods. In Saccharomyces cerevisiae, the production of OA had been previously achieved by rational engineering of the fatty acid synthase. For the supply of the precursor molecule acetyl-CoA and of the redox cofactor NADPH, the native pyruvate dehydrogenase bypass had been harnessed, or the cells had been additionally provided with a pathway involving a heterologous ATP-citrate lyase. Here, we redirected the flux of glucose towards the oxidative branch of the pentose phosphate pathway and overexpressed a heterologous phosphoketolase/phosphotransacetylase shunt to improve the supply of NADPH and acetyl-CoA in a strain background with abolished OA degradation. We show that these modifications lead to an increased yield of OA during the consumption of glucose by more than 60% compared to the parental strain. Furthermore, we investigated different genetic engineering targets to identify potential factors that limit the OA production in yeast. Toxicity assays performed with the engineered strains suggest that the inhibitory effects of OA on cell growth likely impose an upper limit to attainable OA yields.
Metadaten
Author:Florian Wernig, Leonie Baumann, Eckhard Boles, Igor-Mislav OrebORCiDGND
URN:urn:nbn:de:hebis:30:3-638948
DOI:https://doi.org/10.1002/bit.27814
ISSN:1097-0290
Parent Title (English):Biotechnology & bioengineering
Publisher:Wiley
Place of publication:New York, NY [u.a.]
Document Type:Article
Language:English
Date of Publication (online):2021/05/18
Date of first Publication:2021/05/18
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2022/04/05
Tag:acetyl-CoA; octanoic acid; phosphoketolase; phosphotransacetylase
Volume:118
Issue:8
Page Number:12
First Page:3046
Last Page:3057
Note:
This project has received funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 720824.
HeBIS-PPN:494567740
Institutes:Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universit├Ątspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0