Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum

Tessa Moses; Jacob Pollier; Lorena AlmagroDieter BuystMarc Van MontaguMaría A. Pedre?oJosé C. MartinsJohan M. TheveleinAlain Goossens

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Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum

机译：Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum

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The saikosaponins comprise oleanane- and ursane-type triterpene saponins that are abundantly present in the roots of the genus Bupleurum widely used in Asian traditional medicine. Here we identified a gene, designated CYP716Y1, encoding a cytochrome P450 monooxygenase from Bupleurum falcatum that catalyzes the C-16α hydroxylation of oleanane- and ursane-type triterpenes. Exploiting this hitherto unavailable enzymatic activity, we launched a combinatorial synthetic biology program in which we combined CYP716Y1 with oxidosqualene cyclase, P450, and glycosyltransferase genes available from other plant species and reconstituted the synthesis of monoglycosylated saponins in yeast. Additionally, we established a culturing strategy in which applying methylated β-cyclodextrin to the culture medium allows the sequestration of heterologous nonvolatile hydrophobic terpenes, such as triterpene sapogenins, from engineered yeast cells into the growth medium, thereby greatly enhancing productivity. Together, our findings provide a sound base for the development of a synthetic biology platform for the production of bioactive triterpene sapo(ge)nins.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第4期|1634-1639|共6页
作者
Tessa Moses; Jacob Pollier; Lorena AlmagroDieter BuystMarc Van MontaguMaría A. Pedre?oJosé C. MartinsJohan M. TheveleinAlain Goossens;
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作者单位

Department of Plant Systems Biology, VIB, 9052 Gent, Belgium;

Department of Plant Biology, Faculty of Biology, Universidad de Murcia, 30100 Murcia, Spain;

Department of Organic Chemistry, Ghent University, 9000 Gent, BelgiumDepartment of Molecular Microbiology, VIB, 3001 Leuven-Heverlee, Belgium;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
cyclodextrin; amyrin; metabolic engineering; triterpenoid;

Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum

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