Bacillomycin D 复合酶系重组介导的新型抗菌脂肽合成规律探索

利用组合生物学技术对NRPS复合酶进行修饰合成性能优异的抗菌脂肽，近年来一直是国内外关注的热点。我们在前期研究中确定：B.subtilis fmbJ产生的抗菌脂肽BacillomycinD抑真菌、抗肿瘤和抗氧化能力非常强，是目前鉴定的唯一由微生物产生的抑制黄曲霉菌的物质。BacillomycinD由PKS/NRPS合成酶系催化形成，该杂合酶修饰研究尚属新领域。基于此，本项目将揭示: 1)PKS修饰介导的BacillomycinD 脂肪酸链组成与生物活性之间的关系; 2)BacillomycinD合成酶中A结构域和TE结构域的底物选择特异性和作用规律; 3)亚基和模块的变化对BacillomycinD杂合酶结构和功能的影响; 4)COM结构域的修饰与BacillomycinD中酶亚基之间的互作和兼容规律。研究成果将为广谱高效脂肽型食品防腐剂的生物合成奠定理论基础。

It has been the attention focus at home and abroad that using re-combinatorial biotechnology modify the molecular structure of NRPS complex enzyme, and synthesize antimicrobial peptide with excellent property. Our previous studies identified that Bacillomycin D produced by Bacillus subtilis fmbJ have antifungal, antitumor and antioxidant properties, and it is the only one of lipopeptide.originated from microorganism that inhibits Aspergillus flavus. Bacillomycin D is formed by polyketide synthetase (PKS) and non-ribosomal synthase (NRPS) and it is still a new research field for the modification of PKS/NRPS hybrid enzymes. Based on this, this study will explore: 1)The relationship between fatty chain composition and biological activity of Bacillomycin D mediated by PKS modification; 2)Substrate specificity and action law of A domain and TE domain in Bacillomycin D synthetase; 3)Effect of subunit and module change on structure and function of Bacillomycin D hybrid enzymes; 4)The interaction and compatibility law between enzyme subunits in NRPS and modification of COM domain.The research results would provide a theory foundation for the biosynthesis of lipopeptide-type food preservative with high antimicrobial activity and broad spectrum.