Yansheng Zhan

Biography

Education and Appointments： 04/2010-present Professor/Principal Investigator, Wuhan Botanical Garden, Chinese Academy of Sciences, Moshan, Wuhan, 430074, China 04/2008-03/2010 Research Associate, National Research Council Canada, Plant Biotechnology Institute, Sasakatoon, SK, S7NOW9, Canada 04/2006-03/2008 Postdoctoral fellow, National Research Council Canada, Plant Biotechnology Institute, Sasakatoon, SK, S7NOW9, Canada 04/2005-03/2006 Postdoctoral fellow, Donald Danforth Plant Science Center, St. Louis, MO, 63132, United States 09/2001-03/2005 Ph.D, Department of molecular and developmental biology, Institute of Botany, Chinese Academy of Sciences

Research Interest

There is a fantastic resource of medicinal plants in china, many compounds extracted from these plant materials show great pharmacological activities, unfortunately, the supplies of some high value plant metabolites are very limited in natural plant hosts. Cell cultures and chemical synthesis approaches have been applied to the productions of these compounds with a very limited success, especially for the compound with a complicated structure, classical examples are anti-cancer drug “taxol” and anti-malarial drug “artemisinin”, both of them are biosynthesized at a very low level in plants, cell culture systems are disappointing for the productions and chemical synthesis with too many steps are time-consuming and give a overall low yield. Our lab focuses on solving the supply problem through plant molecular biology and synthetic biology. Gene discovery and natural product biosynthesis For gene discovery, we firstly create genomic, proteomic, and metabolomic datasets that will guide us to dig up the genes involved in natural product biosynthesis. For example, we prepare cDNA samples from the specialized cells in which the compounds of interest are produced, create thousands of expressed sequence tags (ESTs) by sequencing cDNAs, and compare the omics data (transcriptomics, proteomics, and metabolomics) from the targeted cell types that are non-treated and treated by elicitors which trigger the biosynthesis of interested compounds. Through the ESTs coupled with omics data, we identify the cDNA candidates that may encode enzymes of interests. We test the cDNA candidates in biochemistry through expressing the candidates heterologously in E.coli and yeast cells, or test their functions in native plant hosts using artificial RNAi technologies. After isolating all the genes in a pathway, we will metabolically engineer the biosynthesis of plant derived drugs in yeast through the stepwise reconstitution of biosynthetic genes in yeast cells, which we called synthetic biology. For the metabolic engineering, there are two major points we need to consider: (1) optimize plant biosynthetic genes and enzymes to facilitate highly expressions of plant natural product biosynthetic pathway in yeast cells, (2) to engineer a yeast platform that can efficiently produce plant derived drugs with potentially commercial applications. We usually synthesize plant biosynthetic genes based on a yeast preferred codon usage and rationally mutate plant biosynthetic enzymes for the applications in yeast cells. We propose to develop a yeast strain that maximize the precursor supply and highly secrete plant derived drugs biosynthesized. We will utilize an in silico analysis to identify gene deletions and gene overexpressions that can enhance precursor supply based on a yeast genome-scale metabolic network model, and then genetically modify the yeast strain based on the analysis results. We also will try to enhance the secretions of plant natural products from yeast cells by genetically engineering yeast metabolite efflux pumps such as ABC transporters. Currently, we are investigating the genes involved in the biosynthesis of isoflavonoids and triterpenoids in several chinese medicinal plant species and metabolically engineering the production of a sesquiterpene (dihydroartemisinic acid originated from artemisia annua plant) in yeast cells at a lab-scale.