The alarming rise in drug-resistant clinical cases of tuberculosis (TB) has necessitated the rapid development of newer chemotherapeutic agents with novel mechanisms of action. The mycobactin biosynthesis pathway, conserved only among the mycolata family of actinobacteria, a group of intracellularly surviving bacterial pathogens that includes Mycobacterium tuberculosis, generates a salicyl-capped peptide mycobactin under iron-stress conditions in host macrophages to support the iron demands of the pathogen. This in vivo essentiality makes this less explored mycobactin biosynthesis pathway a promising endogenous target for novel lead-compounds discovery. In this Perspective, we have provided an up-to-date account of drug discovery efforts targeting selected enzymes (MbtI, MbtA, MbtM, and PPTase) from the mbt gene cluster (mbtA-mbtN). Furthermore, a succinct discussion on non-specific mycobactin biosynthesis inhibitors and the Trojan horse approach adopted to impair iron metabolism in mycobacteria has also been included in this Perspective.

中文翻译：

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霉菌素的生物合成途径：对抗结核病的预期治疗目标

结核病（TB）耐药性临床病例的惊人增加，使得必须快速开发具有新颖作用机制的新型化疗药物。仅在包括结核分枝杆菌在内的一组细胞内存活细菌病原体的放线菌的霉菌家族中，霉菌素的生物合成途径才得以保留，它在宿主巨噬细胞中的铁胁迫条件下产生了水杨基封端的肽霉菌素，以支持病原体的铁需求。这种体内必要性使这种探索较少的分支杆菌素生物合成途径成为新型铅化合物发现的有希望的内源性靶标。在此《观点》中，我们提供了针对mbt基因簇（mbtA-mbtN）中选定的酶（MbtI，MbtA，MbtM和PPTase）的药物发现工作的最新资料。此外，在此观点中还简要讨论了非特异性分枝杆菌素的生物合成抑制剂和特洛伊木马方法，以削弱分枝杆菌中铁的代谢。