Engineer yeast to produce medicinal monoterpene indole alkaloids
发布时间 :2022-09-26  阅读次数 :8457


The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

BioInnovation Institute, Denmark






2011年于瑞典查尔姆斯理工大学获得系统生物学博士学位,师从Jens Nielsen院士,主要研究酿酒酵母中碳源和能量代谢网络的调控。随后在美国麻省理工学院进行博士后研究,主要课题为癌细胞的中心代谢途径及肿瘤分子标志物。2014年开始作为研究员加入丹麦技术大学(Technical University of Denmark)诺和诺德基金会生物可持续性研究中心(Novo Nordisk Foundation Center for Biosustainability)以及丹麦生物创新研究所(BioInnovation Institute),主导酵母的合成生物学元器件开发,转录因子类生物传感器的设计及其在植物天然产物代谢工程领域的应用。在Nature, Nat Chem Biol, Nat Comm, Nucleic Acids Res, Mol Syst Biol, Metab Eng, ACS Synth Biol 等杂志发表高水平学术论文20余篇。



Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including anti-cancer, anti-hypertensive, anti-malarial, anti-addiction, analgesic, etc. As MIAs are difficult to chemically synthesize, their supply is exclusively dependent on plant extraction, which is vulnerable to factors such as plant diseases, natural disasters, pandemics and interruptions in global logistics. For example, a shortage of the chemotherapeutics vinblastine and vincristine has interrupted the cancer treatments of many children patients, because no alternative medicines are available. To establish an alternative source of these medicinal alkaloids independent of their natural plant producers, we engineered the baker’s yeast S. cerevisiae to produce strictosidine, a common precursor of all MIAs. We also demonstrate the biosynthesis of vindoline and catharanthine using yeast fermentation, and chemically coupled them to produce the anti-cancer drug vinblastine. In principle, similarly engineered yeast strains could produce more than 3,000 natural MIAs and their unnatural analogues.