中文摘要
微生物次级代谢过程所产生的天然产物是构成当今拓展战略性新兴产业的庞大生物资源库的重要组成部分。近10年来,申请人一直从事微生物次级代谢产物的生物合成机制研究,并做出了系统的、有创新性的工作:克隆和鉴定了一批结构新颖的微生物次级代谢产物(主要是生物碱类)的生物合成基因簇;发现并阐明了多个新颖的微生物次级代谢过程的酶催化反应及其分子机制,建立了以偶联小分子的载体蛋白为底物的酶学研究方法;利用基因工程技术实现了对原次级代谢产物的结构改造。这些研究成果为深入揭示微生物次级代谢的分子机制,构建生物元件库及人工设计合成新的生物资源奠定了基础。迄今,共发表论文60篇,其中51篇被SCI收录。近5年, 在包括PNAS, JACS, Angew Chem Int Ed, JBC, and ChemBioChem等期刊发表SCI论文31篇。多次受邀在国际或国内会议上做学术报告。
英文摘要
Natural products produced by microbial secondary metabolism constitute an important part of the vast repository of biological resources to develop strategic emerging industries nowadays. In the past nearly 10 years, the applicant has made a series of systematic and innovative work in the field of molecular mechanisms of microbial secondary metabolism: (1) Several biosynthetic gene clusters of microbial secondary metabolites (mainly microbial alkaloids) with novel structures have been cloned and characterized, and as well as their biosynthetic models have been established; (2) By means of combination of organic chemistry and biology, numbers of novel microbial enzymatic reactions and their molecular mechanisms involved in secondary metabolic processes have been discovered and clarified, and the methodology used to study the enzymatic reactions with carrier protein-tethered substrate has been established; (3) Genetic engineering techniques were used to achieve the structural modifications of secondary metabolites and create their structural diversities. These results set a solid foundation for deeply revealing the molecular mechanism of microbial secondary metabolism, constructing the laboratory of biological components and designing artificial biological pathways to create new biological resources. Up to today, 60 papers have been published, 51 of which were cited by SCI. In the past five years, 31 papers have been published in the SCI-cited journals including PNAS, JACS, Angew Chem Int Ed, JBC and ChemBioChem etc. The applicant has been invited to give important talks in many international or domestic conferences.
