Improvement of betulinic acid biosynthesis in yeast employing multiple strategies

BMC Biotechnology

Research Article

Yansheng Zhang¹  Changfu Li¹  Chen Zhou²  Jing Li² 

[1] CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, 430074, Wuhan, China;CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, 430074, Wuhan, China;University of Chinese Academy of Sciences, 100049, Beijing, China;

关键词: Betulinic acid;    Betulin;    Biosynthesis;    Saccharomyces cerevisiae;   

DOI  :  10.1186/s12896-016-0290-9

 received in 2016-01-18, accepted in 2016-08-09,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundBetulinic acid (BA) is a lupane-type triterpene which has been considered as a promising agent to cure melanoma with no side effects. Considering that BA is naturally produced in small quantities in plants, we previously reported the success in engineering its production in yeast. In the present study, we attempted to improve BA biosynthesis in yeast by the use of different strategies.ResultsWe first isolated a gene encoding a lupeol C-28 oxidase (LO) from Betula platyphylla (designated as BPLO). BPLO showed a higher activity in BA biosynthesis compared to the previously reported LOs. In addition, two yeast platforms were compared for engineering the production of BA, which demonstrated that the WAT11 strain was better to host BA pathway than the CEN.PK strain. Based on the WAT11-chassiss, the Gal80p mutant was further constructed. The mutant produced 0.16 mg/L/OD600 of BA, which was 2.2 fold of that produced by the wild type strain (0.07 mg/L/OD600).ConclusionsThis study reported our efforts to improve BA production in yeast employing multiple strategies, which included the identification of a novel LO enzyme with a higher activity in BA biosynthesis, the evaluation of two yeast strains for hosting the BA pathway, and the up-regulation of the expression of the BA pathway genes by managing yeast GAL gene regulon circuit.

【 授权许可】

CC BY   
© The Author(s). 2016