报告题目：Novel transformations in alkaloid biosynthesis catalyzed by iron-enzymes

报告人：刘平华教授

报告人单位：美国波士顿大学

报告时间：2017年5月17日（周三），15:00-17:00

报告地点：18号实验楼315室

报告人简介：

   美国波士顿大学，化学系，教授

The Liu Group’s research is at the interface of Chemistry and Biology. Their work focuses on：

(a) Mechanistic studies and the application of pharmacologically important natural products using organic, molecular biology as well as biophysical methods.

(b) The chemical basis of biological clock with the ultimate goal of elucidating the time-recording mechanism in the ageing process. Their work’s main focuses are the chemical basis of pathogen and host interactions, and the chemical nature of the biological clock. 

His projects address two major areas:

(1) Mechanistic studies of two metallo-proteins (IspG and IspH) in the corresponding process;

(2) Identification of other components in these two processes.

The techniques & resources in Liu’s Lab are summarized as below:

Enzymology: This includes organic synthesis, synthesis of isotopically labeled probes, sub-cloning, protein expression and purification, steady-state and pre-steady state kinetics, inhibitor design and evaluation, and mechanistic studies.

Genetics: The Liu lab uses transcriptional, post-transcriptional, and post-translational regulation, gene knockout, gene replacement, and metabolic engineering.

Spectroscopies: EPR and Mössbauer for metallo-enzyme characterizations are utilized in the lab.

报告摘要

  Novel transformations in alkaloid biosynthesis catalyzed by iron-enzymes

Activation of C-H bond for C-C bond and C-X bond formation has inspired generations of synthetic organic and biosynthetic chemists. In the last decades, many precious metal-based (e.g., Ru, Rh, Ir, Pd) catalytic systems have been developed. Interestingly, in biological systems, other more readily available metals (e.g., Fe, Co, Cu) are normally used, and the reactions are accomplished under very mild conditions (room temperature and regular pressure) and in aqueous medium. In this presentation, we will discuss our recent efforts on iron-enzyme catalyzed novel transformations: oxidative C-S bond formation and the activation of molecular oxygen to form endoperoxide.

Production of high value product through synthetic biology: Natural products are still one of the major sources of human medicine. However, for many natural products, due to their complicated structures, fermentation-based production is still the most competitive approach. I will present our mechanistic studies of two unprecedented C-S bond construction reactions, and then how these mechanistic study efforts guide our efforts to achieve high yield production of two high value products (billion dollar market size) through fermentation.

Iron-enzyme catalyzed endoperoixde formation.Over the years, many peroxy-containing secondary metabolites have been isolated from plants, marine invertebrates, particularly in sponge species. Among them, artemisinin was clinically applied in antimalarial therapies, and many other organic peroxides show anti-cancer and antibacterial activities.  Thus far, the only characterized enzyme for endoperoxide formation is a heme-containing prostaglandin H synthase. In this talk, I will present the first non-heme iron enzyme catalyzed endoperoxide formation reaction.