新药物分子的发现、合成及功能研究是药学学科的核心基础问题之一。申请人围绕上述问题作出了一些有创新意义的成绩：运用无保护基策略高效不对称全合成了石松生物碱lannotinidine B；成功地使用不同的策略包括诱导沉默基因的表达、基因敲除及前体饲喂等方法组合生物合成了多种类型的活性复杂化合物；深入研究了多个属种的特境微生物以及热带龙脑香科植物的次级代谢产物，发现了一批结构新颖、活性显著的天然产物，揭示了相关物种的活性物质基础与作用特点。建立的方法和有关数据对相关研究具有重要参考价值，也为天然药物的研发提供了新线索。申请人已在《美国科学院院报》、《美国化学会志》、《化学通讯》等国际核心刊物发表SCI 论文77篇，论文共被SCI引用1037篇次，他引872篇次。本项目拟重点对特境微生物所产次级代谢产物的化学生物学进行研究，进而探索这些天然产物在药学等领域的应用。

One of the key issues in pharmaceutical science is the discovery, synthesis, and biological study of novel natural products. Focusing on this issue, several innovative results have been achieved by the applicant and coworkers, including: a highly efficient and asymmetric total synthesis of a lycopodium alkaloid lannotinidine B with a non-protecting group strategy; the combinatorial biosynthesis of several "unnatural" natural products with different skeletons using different strategy including expression of silent genes, gene inactivation and precursor feeding experiments; the discovery of lots of natural products with novel scaffold and/or potent bioactivities from microbes lived in the special niche or tropical Dipterocarpus plants, which disclose the bioactive substances of these species. The finding could be very useful for the relevant studies and also will supply some new clues for the drug development. So far, the applicant has been co-authored 77 papers in the SCI peer-reviewed journals such as PNAS, JACS, Chem Commun, et al. According to the statistic from Web of Sciences , these publications have been cited for 1037 times (872 by others). In this project, we will focus our study on chemical biology of the natural products from microbes lived in special niche.