期刊
PLANT COMMUNICATIONS
卷 2, 期 1, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.xplc.2020.100079
关键词
metabolic engineering; genomic evolution; diosgenin; synthetic biology
资金
- National Key R&D Program of China [2019YFA0905700, 2019YFA0905300]
- Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project [TSBICIP-KJGG-002]
- Key Research Program of the Chinese Academy of Sciences [KFZD-SW-215]
- Tianjin Science Fund for Distinguished Young Scholars [18JCJQJC48300]
- National Science and Technology Major Project [2018ZX09711001-006-003]
- Major Science and Technique Programs in Yunnan Province [2019ZF011]
- National Science Fund for Excellent Young Scholars [31922047]
This study sequenced the whole genome of Dioscorea species to reveal the evolutionary trajectory of the diosgenin biosynthetic pathway. It demonstrated de novo biosynthesis of diosgenin in a yeast cell factory. The study also introduced an alternative approach for the production of diosgenin through synthetic biology by integrating genes from plants, animals, and yeast.
Diosgenin, mainly produced by Dioscorea species, is a traditional precursor of most hormonal drugs in the pharmaceutical industry. The mechanisms that underlie the origin and evolution of diosgenin biosynthesis in plants remain unclear. After sequencing the whole genome of Dioscorea zingiberensis, we revealed the evolutionary trajectory of the diosgenin biosynthetic pathway in Dioscorea and demonstrated the de novo biosynthesis of diosgenin in a yeast cell factory. First, we found that P450 gene duplication and neo-functionalization, driven by positive selection, played important roles in the origin of the diosgenin biosynthetic pathway. Subsequently, we found that the enrichment of diosgenin in the yam lineage was regulated by CpG islands, which evolved to regulate gene expression in the diosgenin pathway and balance the carbon flux between the biosynthesis of diosgenin and starch. Finally, by integrating genes from plants, animals, and yeast, we heterologously synthesized diosgenin to 10 mg/l in genetically-engineered yeast. Our study not only reveals the origin and evolutionary mechanisms of the diosgenin biosynthetic pathway in Dioscorea, but also introduces an alternative approach for the production of diosgenin through synthetic biology.
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