title: Opportunities and challenges from current investigations into the biosynthetic logic of nosiheptide-represented thiopeptide antibiotics.
abstract: Nosiheptide is an archetypal thiopeptide antibiotic, possessing a characteristic macrocyclic core that contains a 6-membered heterocycle central to multiple azol(in)es and dehydroamino acids. The discovery of the ribosomal origin of thiopeptides revealed a unifying theme, showing that the structural complexity arises from post-translational modifications (PTMs) of precursor peptides. Thiopeptide framework formation proceeds via cyclodehydration/dehydrogenation (for azol(in)es), dehydration (for dehydroamino acids), and cycloaddition (for the central heterocycle domain). This common process has not been reproduced in vitro, partly due to the poorly understood logic of thiopeptide biosynthetic pathways. Utilizing nosiheptide biosynthesis as a model system, we herein consider how nature coordinates a number of highly interwined, common and specific PTMs to accomplish the complexity of ribosomally synthesized and post-translationally modified peptides.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Shoufeng
authors.initials: S
authors.lastname: Wang
authors.forename: Shuaixiang
authors.initials: S
authors.lastname: Zhou
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D061565:Cycloaddition Reaction; D006865:Hydrogenation; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D013844:Thiazoles; C014134:nosiheptide