深海来源微生物中Siderophore类化合物的发掘及生物合成研究

抗生素耐药性已成为全球最主要的健康问题，不断增加的抗生素耐药性可能威胁到外科手术的安全性、有效性和免疫抑制的化疗效果，抗生素耐药性问题迫切需要解决。微生物分泌的一种能和铁离子螯合的Siderophore（嗜铁素）类成分，可与抗生素耦合选择性地与病原微生物细胞膜表面的嗜铁素外膜受体发生相互作用，将药物释放到细胞中杀死微生物，进而发挥抗菌作用。这种“特洛伊木马”策略在传递药物分子方面具有广阔的应用前景。本项目利用嗜铁素类成分独特的铬天青S（Chrome azurol S，CAS）活性，采用CAS活性和LC-MS排重双模型筛选方法及基因组挖掘技术，实现3株深海微生物中新型嗜铁素的筛选和生物合成研究，为后期嗜铁素-抗生素耦合物的研发奠定理论基础，对解决细菌的耐药性问题具有前瞻性和新颖性。

Antibiotic resistance has been emerged as a major global health problem, increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy, novel approaches to this issue are urgently required. Microogranisms can secrete a kind of siderophore molecules to chelate iron ion in the environment. Therefore, the siderophore-anibiotic conjugates can selectively bind with siderophore outer membrane receptor on the surface of the pathogenic microbiology cell membrane, and transport the drugs into the cell to kill pathogenic microbiology. The Trojan horse trickery approach has broad application prospects in the delivery of bioactive drug molecules. This project will utilize characteristic Chrome Azurol S activity of siderophores, coupled with LC-MS dual model and genome mining for secondary metabolites, to discover novel siderophores from 3 marine microorganisms and study theirbiosynthesis mechanism. This study will provide a theoretical basis for the later development of siderophore-drug conjugates and has obviously advance and novelty for solving bacterial resistance problem.