抗体偶联药物（antibody drug conjugates, ADC）是当前抗肿瘤药物研究的热点，而偶联分子是其成药关键。烯二炔由于具有超高的抗肿瘤活性，自然成为ADC的理想分子物。迄今全球只发现了11个烯二炔天然产物，两个已开发成药。如何利用基因组挖掘，通过生物合成技术，获得结构新颖、理化性质和生物活性更好的烯二炔天然产物，将对整个ADC药物研发领域产生重大的影响。.. 根据我们的前期研究成果，对4889个微生物的基因信息挖掘发现，7%的放线菌含有烯二炔生物合成基因簇，为从放线菌中发现新颖烯二炔天然产物奠定了遗传基础。本课题将通过对自建放线菌菌种资源库进行烯二炔基因探矿和生物合成研究，获得2-5个新颖的烯二炔天然产物，为我国原创ADC新药开发提供更多的偶联药物，并通过与已知烯二炔生物合成机制的比较研究，揭示烯二炔核心形成的精细催化机制。

Most major pharmaceutical companies have an oncology program named antibody drug conjugates (ADC)，owing to the successful launch of two ADCs, Adcetris® in 2011 and Kadcyla® in 2013. The enediyne natural products are the most cytotoxic molecules in existence today, and their use as anticancer drugs in ADCs has been demonstrated clinically while there are only 11 enediynes known to date. The ADC field is in critical need of new, highly potent cytotoxic payloads, and an increasing inventory of enediynes would benefit current application of ADCs in many oncology programs... Bioinformatics analysis of genes and gene clusters from 4889 microbial species reveals that enediynes are underexplored, in particular that around 7% Actinomycetal genomes contain enediyne biosynthetic gene clusters. In order to discover novel enediyne natural products, genome mining of our Actinomycetal collection is proposed. The detailed biosynthetic mechanisms of enediyne core would hopefully be deciphered and 2-5 novel enediynes useful in ADCs would be expected.