HSAF是生防细菌产酶溶杆菌产生的一种对病原真菌、卵菌具有广谱拮抗活性的次级代谢抗菌物质，具有被开发为生物农药的潜力，但产量低限制了其产业化发展。在明确其调控机制的基础上，通过遗传改良获得高产菌株是目前提高HSAF产量的有效方法。申请者近期从产酶溶杆菌OH11中发现了一个负向调控HSAF生物合成的环二鸟苷酸(c-di-GMP)合成酶LchD。c-di-GMP是细菌中的新型第二信使，参与调控病原细菌致病性、生物膜合成等重要生理生化功能，但对生防细菌中抗菌物质调控方面的研究较少。因此，本课题将综合运用生物信息学、遗传学和分子生物学等手段，研究LchD的生物学功能，鉴定LchD介导的c-di-GMP调控HSAF合成的信号通路，解析LchD调控HSAF生物合成的分子机制。课题研究成果不仅可以揭示c-di-GMP调控次生代谢抗菌物质的分子机制，也将为遗传改良获得HSAF高产菌株供理论依据。

Lysobacter enzymogenes is an environmentally friendly and important biocontrol agent. HSAF is a kind of secondary metabolite antimicrobial substance produced by L. enzymogenes with broad-spectrum antagonistic activity against many pathogenic fungi and oomycetes. Thus, HSAF has the potential application as a bio-pesticide. However, the low production of HSAF limits its industrialization. At present, obtaining HSAF high yield strains by genetic modification based on its regulation mechanism is an effective method to increase HSAF yield. We have recently identified a c-di-GMP synthase LchD, which negatively regulates HSAF biosynthesis in L. enzymogenes OH11, but its regulation mechanism is unknown. The second messenger c-di-GMP is a hotspot in bacteria research in recent years. It can regulate pathogenicity, biofilm formation, cell cycle and other important physiological and biochemical functions in pathogenic bacteria, while less is known in biocontrol bacteria, especially for regulation in secondary metabolic antimicrobial substances. To this end, we will use bioinformatics, genetics and molecular biology to study the function of LchD in c-di-GMP synthesis and HSAF biosynthesis, to identify a LchD-c-di-GMP-receptor signaling pathway and to demonstrate the molecular mechanism of LchD in regulating HSAF biosynthesis. The results not only can reveal the molecular mechanism of c-di-GMP regulating secondary metabolites, but also provide theoretical basis for obtaining HSAF high yield strains for genetic improvement.