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Production of octanoic acid in Saccharomyces cerevisiae : Investigation of new precursor supply engineering strategies and intrinsic limitations
- Source :
- Biotechnology and Bioengineering
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- 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.
- Subjects :
- 0106 biological sciences
0301 basic medicine
Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae
Phosphoketolase
Bioengineering
Pentose phosphate pathway
01 natural sciences
Applied Microbiology and Biotechnology
03 medical and health sciences
chemistry.chemical_compound
ddc:570
010608 biotechnology
chemistry.chemical_classification
biology
Acetyl-CoA
Fatty acid
Lyase
biology.organism_classification
Fatty acid synthase
030104 developmental biology
Metabolic Engineering
Biochemistry
chemistry
biology.protein
Caprylates
Flux (metabolism)
Biotechnology
Subjects
Details
- ISSN :
- 10970290 and 00063592
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- Biotechnology and Bioengineering
- Accession number :
- edsair.doi.dedup.....f80701c32a720cb949a6a68c9dd55b22