Green production of silybin and isosilybin by merging metabolic engineering approaches and enzymatic catalysis

Silymarin extracted from milk thistle seeds, is used for treating hepatic diseases. Silybin and isosilybin are its main components, and synthesized from coupling of taxifolin and coniferyl alcohol. Here, the biosynthetic pathways of taxifolin and coniferyl alcohol were reconstructed in Saccharomyces...

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Bibliographic Details
Published in:Metabolic engineering 2020-05, Vol.59, p.44-52
Main Authors: Yang, Jiazeng, Liang, Jincai, Shao, Lei, Liu, Lihong, Gao, Ke, Zhang, Jun-Liang, Sun, Zhenjiao, Xu, Wendong, Lin, Pengcheng, Yu, Rongmin, Zi, Jiachen
Format: Article
Language:English
Subjects:
Coniferyl alcohol
Enzymatic catalysis
Metabolic Engineering
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Silybin
Silybin - metabolism
Silymarin - analogs & derivatives
Silymarin - metabolism
Taxifolin
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Summary:Silymarin extracted from milk thistle seeds, is used for treating hepatic diseases. Silybin and isosilybin are its main components, and synthesized from coupling of taxifolin and coniferyl alcohol. Here, the biosynthetic pathways of taxifolin and coniferyl alcohol were reconstructed in Saccharomyces cerevisiae for the first time. To alleviate substantial burden caused by a great deal of genetic manipulation, expression of the enzymes (e.g. ZWF1, TYR1 and ARO8) playing multiple roles in the relevant biosynthetic pathways was selectively optimized. The strain YT1035 overexpressing seven heterologous enzymes and five native enzymes and the strain YC1053 overexpressing seven heterologous enzymes and four native enzymes, respectively produce 336.8 mg/L taxifolin and 201.1 mg/L coniferyl alcohol. Silybin and isosilybin are synthesized from taxifolin and coniferyl alcohol under catalysis of APX1t (the truncated milk thistle peroxidase), with a yield of 62.5%. This study demonstrates an approach for producing silybin and isosilybin from glucose for the first time. •Yeast was engineered for producing taxifolin and coniferyl alcohol, respectively.•A total of 21 exogenous genes were tested in yeast.•Overexpression of the native genes with dual roles dramatically enhanced the titers.•Taxifolin and coniferyl alcohol were rapidly purified by a green process.•Silybin and isosilybin were synthesized by enzymatic catalysis.
ISSN:1096-7176
1096-7184
DOI:10.1016/j.ymben.2020.01.007