Institute of Life Science, College of Medicine, Swansea University, Swansea, Wales, United Kingdom.
Institute of Life Science, College of Medicine, Swansea University, Swansea, Wales, United Kingdom.
Adv Appl Microbiol. 2014;89:217-66. doi: 10.1016/B978-0-12-800259-9.00006-8.
The actinomycetes are well-known bioactive natural product producers, comprising the Streptomycetes, the richest drug-prolific family in all kingdoms, producing therapeutic compounds for the areas of infection, cancer, circulation, and immunity. Completion and annotation of many actinomycete genomes has highlighted further how proficient these bacteria are in specialized metabolism, which have been largely underexploited in traditional screening programs. The genome sequence of the model strain Streptomyces coelicolor A3(2), and subsequent development of genomics-driven approaches to understand its large specialized metabolome, has been key in unlocking the high potential of specialized metabolites for natural product genomics-based drug discovery. This review discusses systematically the biochemistry and genetics of each of the specialized metabolites of S. coelicolor and describes metabolite transport processes for excretion and complex regulatory patterns controlling biosynthesis.
放线菌是众所周知的生物活性天然产物产生菌,包括链霉菌,这是所有生物界中最富有药物生产力的家族,产生用于感染、癌症、循环和免疫领域的治疗化合物。许多放线菌基因组的完成和注释进一步强调了这些细菌在特殊代谢方面的能力,而这些能力在传统的筛选计划中很大程度上未被充分利用。模式菌株变红红链霉菌 A3(2)的基因组序列,以及随后发展的基于基因组学的方法来理解其大型特殊代谢组,对于释放特殊代谢物在基于天然产物基因组学的药物发现中的高潜力至关重要。本文系统地讨论了变红红链霉菌的每种特殊代谢物的生物化学和遗传学,并描述了代谢物的排泄转运过程和复杂的调控模式控制生物合成。