Journal
MICROBIAL BIOTECHNOLOGY
Volume 14, Issue 6, Pages 2627-2642Publisher
WILEY
DOI: 10.1111/1751-7915.13880
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Funding
- CSIRO Synthetic Biology Future Science Fellowship
- University of Queensland
- Indonesia Endowment Fund for Education scholarship
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By introducing heterologous acetyl-CoA pathways and Mig1p degradation, the production efficiency of nerolidol was improved. However, superior heterologous enzymes are needed to fully establish functional synthetic acetyl-CoA pathways.
The yeast Saccharomyces cerevisiae uses the pyruvate dehydrogenase-bypass for acetyl-CoA biosynthesis. This relatively inefficient pathway limits production potential for acetyl-CoA-derived biochemical due to carbon loss and the cost of two high-energy phosphate bonds per molecule of acetyl-CoA. Here, we attempted to improve acetyl-CoA production efficiency by introducing heterologous acetylating aldehyde dehydrogenase and phosphoketolase pathways for acetyl-CoA synthesis to enhance production of the sesquiterpene trans-nerolidol. In addition, we introduced auxin-mediated degradation of the glucose-dependent repressor Mig1p to allow induced expression of GAL promoters on glucose so that production potential on glucose could be examined. The novel genes that we used to reconstruct the heterologous acetyl-CoA pathways did not sufficiently complement the loss of endogenous acetyl-CoA pathways, indicating that superior heterologous enzymes are necessary to establish fully functional synthetic acetyl-CoA pathways and properly explore their potential for nerolidol synthesis. Notwithstanding this, nerolidol production was improved twofold to a titre of similar to 900 mg l(-1) in flask cultivation using a combination of heterologous acetyl-CoA pathways and Mig1p degradation. Conditional Mig1p depletion is presented as a valuable strategy to improve the productivities in the strains engineered with GAL promoters-controlled pathways when growing on glucose.
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