ArticleMicrobial cell factories2022
Enhanced production of amyrin in Yarrowia lipolytica using a combinatorial protein and metabolic engineering approach.
Article in Microbial cell factories, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 20 citations in OpenAlex.
- High-level amyrin production inSynthetic and systems biotechnology · 2027Article
- Advances in the heterologous biosynthesis of QS saponins: a review.Microbial cell factories · 2026Review
- Advances in semi-rational design of terpene synthases and their modifying enzymes.AMB Express · 2025Review
- Combing Directed Enzyme Evolution with Metabolic Engineering to Develop Efficient Microbial Cell Factories.Chem & bio engineering · 2025Review
- Sustainable biosynthesis of squalene from waste cooking oil by the yeastMetabolic engineering communications · 2024Article
- Protein engineering in the computational age: An open source framework for exploring mutational landscapesEngineering biology · 2023Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
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Abstract
backgroundAmyrin is an important triterpenoid and precursor to a wide range of cosmetic, pharmaceutical and nutraceutical products. In this study, we metabolically engineered the oleaginous yeast, Yarrowia lipolytica to produce α- and β-amyrin on simple sugar and waste cooking oil.
resultsWe first validated the in vivo enzymatic activity of a multi-functional amyrin synthase (CrMAS) from Catharanthus roseus, by expressing its codon-optimized gene in Y. lipolytica and assayed for amyrins. To increase yield, prevailing genes in the mevalonate pathway, namely HMG1, ERG20, ERG9 and ERG1, were overexpressed singly and in combination to direct flux towards amyrin biosynthesis. By means of a semi-rational protein engineering approach, we augmented the catalytic activity of CrMAS and attained ~ 10-folds higher production level on glucose. When applied together, protein engineering with enhanced precursor supplies resulted in more than 20-folds increase in total amyrins. We also investigated the effects of different fermentation conditions in flask cultures, including temperature, volumetric oxygen mass transfer coefficient and carbon source types. The optimized fermentation condition attained titers of at least 100 mg/L α-amyrin and 20 mg/L β-amyrin.
conclusionsThe design workflow demonstrated herein is simple and remarkably effective in amplifying triterpenoid biosynthesis in the yeast Y. lipolytica.
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