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Productive Amyrin Synthases for Efficient α-Amyrin Synthesis in Engineered Saccharomyces Cerevisiae

Productive Amyrin Synthases for Efficient α-Amyrin Synthesis in Engineered Saccharomyces Cerevisiae

Yuan Yu, Pengcheng Chang, Huan Yu, Huiyong Ren, Danning Hong, Zeyan Li, Ying Wang, Hao Song, Yixin Huo, Chun Li

ACS Synth Biol. 2018 Oct 19;7(10):2391-2402.

PMID: 30216049

Abstract:

α-Amyrin is a plant-derived pentacyclic triterpenoid, with a lot of important physiological and pharmacological activities. The formation of α-amyrin from (3 S)-2,3-oxidosqualene is catalyzed by α-amyrin synthase (α-AS), a member of the oxidosqualene cyclase (OSC) protein family. However, α-amyrin is not yet commercially developed due to its extremely low productivity in plants. The engineered Saccharomyces cerevisiae with efficient α-amyrin production pathway could be used as an alternative and sustainable solution to produce α-amyrin from renewable raw materials. To efficiently improve α-amyrin production in S. cerevisiae, we identified two α-ASs, EjAS and MdOSC1 from Eriobotrya japonica and Malus × domestica, respectively, through strict bioinformatics screening criteria and phylogenetic analysis. The specific activities of purified EjAS and MdOSC1 were 0.0032 and 0.0293 μmol/min/mg, respectively. EjAS produced α-amyrin and β-amyrin at a ratio of 17:3, MdOSC1 produced α-amyrin, β-amyrin and lupeol at a ratio of 86:13:1, indicating MdOSC1 had significantly higher specific activity and higher ratio of α-amyrin than EjAS. Furthermore, MdOSC1 was introduced into S. cerevisiae combining with the increased supply of (3 S)-2,3-oxidosqualene to achieve the encouraging α-amyrin production, and the titer of α-amyrin achieved 11.97 ± 0.61 mg/L, 5.8 folds of the maximum production reported.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP638959	α-Amyrin		638-95-9	Price

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