放线菌中铁载体生物合成机制研究进展

铁载体是由微生物产生,对铁元素具有高亲和性的小分子化合物。这类天然产物所展现的结构多样性引起人们对其生物合成机制的极大兴趣。目前已有研究报道的铁载体生物合成途径主要有2种,一是直接由非核糖体肽合成酶(Nonribosomal peptide synthetases,NRPSs)家族的多酶复合体负责合成,另一种是以不依赖于NRPS(NRPS-independent,NIS)的方式,由一类特殊合成酶家族参与合成。在过去的十多年中,铁载体生物合成成为天然产物生物合成研究领域的热点之一,其中几种依赖于NRPS途径合成的铁载体生物合成机制已得到充分阐明,而对NIS方式合成的铁载体研究也获得了诸多进展。作为放线菌的一类重要次级代谢产物,通过遗传学、化学等手段对放线菌所产生铁载体生物合成途径的遗传学和生物化学研究,能够为发展新的抗菌药物提供契机,同时也能加深我们对这一类生物活性物质形成机制的认识。综述近期该研究方向的进展。

Recent advances in mechanism of siderophore biosynthesis in actinomycetes

Iron acquisition represents a challenging problem for bacteria because Fe is an essential element with very low bioavailability. Siderophores, produced by microorganisms, are high-affinity ferric iron chelators with attractive structural diversity. Two main pathways for siderophore biosynthesis have been reported. One involves multifunctional metasynthase nonribosomal peptide synthetase (NRPS), while the other is NRPS-independent (NIS) and catalyzed by siderophore synthetase superfamily. Biosynthesis of siderophores has been the focus of inquiry for nearly twenty years. The enzymology of NRPS-mediated biosynthetic pathway of siderophore has been intensively studied and a vast knowledge of the NRPS-independent siderophore (NIS) biosynthesis is increasing. As siderophore is one type of the important secondary metabolites from actinomycetes, genetic and biochemical studies of its biosynthetic pathways will provide an opportunity to develop potential antibacterial agents, and enable the increasing understanding of the biosynthetic mechanism of this kind of natural products as well. Here we summarize the recent progress in mechanism of siderophore biosynthesis.