ArticleJournal of industrial microbiology & biotechnology2021
Engineering acetyl-CoA supply and ERG9 repression to enhance mevalonate production in Saccharomyces cerevisiae.
Article in Journal of industrial microbiology & biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 29 citations in OpenAlex.
- Multi-level metabolic engineering for squalene production: from pathway optimization to systematic regulation.World journal of microbiology & biotechnology · 2026Review
- Review
- The Mevalonate Pathway: Innovations, Applications, and Challenges in Biotechnology with Emphasis on Fungal Biology.Journal of fungi (Basel, Switzerland) · 2026Review
- Advances in microbial mevalonolactone production: from fermentative mevalonate accumulation to downstream lactonization.Engineering microbiology · 2026Review
- Combined metabolic and enzymatic engineering forSynthetic and systems biotechnology · 2025Article
- Orthogonal replication with optogenetic selection evolves yeast JEN1 into a mevalonate transporter.Molecular systems biology · 2025Article
- ATP deficiency triggers ganoderic acids accumulation via fatty acid β-oxidation pathway in Ganoderma lucidum.Microbial cell factories · 2025Article
- Integrative Transcriptomic and Target Metabolite Analysis as a New Tool for Designing Metabolic Engineering in Yeast.Biomolecules · 2024Article
- Microbial production of high octane and high sensitivity olefinic ester biofuels.Biotechnology for biofuels and bioproducts · 2023Article
- Application of cofactors in the regulation of microbial metabolism: A state of the art review.Frontiers in microbiology · 2023Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mevalonate is a key precursor in isoprenoid biosynthesis and a promising commodity chemical. Although mevalonate is a native metabolite in Saccharomyces cerevisiae, its production is challenged by the relatively low flux toward acetyl-CoA in this yeast. In this study we explore different approaches to increase acetyl-CoA supply in S. cerevisiae to boost mevalonate production. Stable integration of a feedback-insensitive acetyl-CoA synthetase (Se-acsL641P) from Salmonella enterica and the mevalonate pathway from Enterococcus faecalis results in the production of 1,390 ± 10 mg/l of mevalonate from glucose. While bifid shunt enzymes failed to improve titers in high-producing strains, inhibition of squalene synthase (ERG9) results in a significant enhancement. Finally, increasing coenzyme A (CoA) biosynthesis by overexpression of pantothenate kinase (CAB1) and pantothenate supplementation further increased production to 3,830 ± 120 mg/l. Using strains that combine these strategies in lab-scale bioreactors results in the production of 13.3 ± 0.5 g/l, which is ∼360-fold higher than previously reported mevalonate titers in yeast. This study demonstrates the feasibility of engineering S. cerevisiae for high-level mevalonate production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.