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.
Author:Florian Wernig, Leonie Baumann, Eckhard Boles, Igor-Mislav OrebORCiDGND
Parent Title (English):Biotechnology & bioengineering
Place of publication:New York, NY [u.a.]
Document Type:Article
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
Page Number:12
First Page:3046
Last Page:3057
This project has received funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 720824.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0