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

Jiazeng Yang, Jincai Liang, Lei Shao, Lihong Liu, Ke Gao, Jun-Liang Zhang, Zhenjiao Sun, Wendong Xu, Pengcheng Lin, Rongmin Yu, Jiachen Zi

Metabolic engineering 2020 May

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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. Copyright © 2020 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Citation

Jiazeng Yang, Jincai Liang, Lei Shao, Lihong Liu, Ke Gao, Jun-Liang Zhang, Zhenjiao Sun, Wendong Xu, Pengcheng Lin, Rongmin Yu, Jiachen Zi. Green production of silybin and isosilybin by merging metabolic engineering approaches and enzymatic catalysis. Metabolic engineering. 2020 May;59:44-52