白黄链霉菌TD-1代谢产生的帕马霉素对黄曲霉及毒素具有良好的抑制作用，但其生物合成、调控机制未被完整解析。项目围绕TD-1菌产生的帕马霉素抑制黄曲霉及黄曲霉毒素B1（AFB1）机制、帕马霉素在TD-1菌中的合成途径、代谢调控机制及提高帕马霉素产量开展研究：①通过黄曲霉形态及能量代谢变化，结合转录组分析等，阐明帕马霉素对黄曲霉及AFB1的拮抗机制；②根据TD-1菌帕马霉素合成前和快速合成阶段的转录组/蛋白组联合分析，结合antiSMASH分析得到的TD-1帕马霉素合成基因簇，采用基因敲除、回补等技术验证基因功能，解析帕马霉素合成、调控机制；③构建TD-1基因组尺度代谢网络模型，预测潜在基因改造靶点，利用基因敲除/过表达等技术构建高效基因工程菌。该项目对阐明TD-1菌产生的帕马霉素对黄曲霉及AFB1拮抗机制、揭示TD-1菌帕马霉素合成、调控机制具有理论意义，对构建高效生防链霉菌具有应用价值。

Pamamycin isolated from Streptomyces alboflavus TD-1 has been found to be able to suppress Aspergillus flavus and aflatoxin contamination which poses great threats to both annual crop losses and human health. However, the antifungal mechanisms as well as the biosynthesis and regulation of pamamycin have not been fully clarified. Therefore, this project aims to 1) reveal the antagonistic mechanism of pamamycin based on morphology changes and energy metabolism of A. flavus in combination with transcriptome analysis; 2) uncover the biosynthesis and regulation mechanism of pamamycin by screening pamamycin-related biosynthetic gene cluster using both proteome/transcriptome and antiSMASH analysis. Functional gene analysis technique will be used to verify gene function in pamamycin biosynthetic and regulatory pathways; 3) establish the genome-scale metabolic network model predicting the potential engineering targets, and to construct the genetic engineering strains for pamamycin production by metabolic engineering technology including the gene knockout and overexpression. This study will not only help to uncover the suppressing mechanisms of pamamycin towards A. flavus and aflatoxin contamination, but also reveal biosynthesis and regulation of pamamycin in S. alboflavus TD-1. Successful delivery of this project will facilitate the development of the recombined strain.