title: Caerulomycins and collismycins share a common paradigm for 2,2'-bipyridine biosynthesis via an unusual hybrid polyketide-peptide assembly Logic.
abstract: Caerulomycins (CAEs) and collismycins (COLs), which mainly differ in sulfur decoration, are two groups of structurally similar natural products containing a 2,2'-bipyridine (2,2'-BP) core, derivatives of which have been widely used in chemistry. The biosynthetic pathways of CAEs and COLs remain elusive. In this work, cloning of the CAE biosynthetic gene cluster allowed us to mine a highly conserved gene cluster encoding COL biosynthesis in a  Streptomyces  strain that was previously unknown as a 2,2'-BP producer. In vitro and in vivo investigations into the biosynthesis revealed that CAEs and COLs share a common paradigm featuring an atypical hybrid polyketide synthase/nonribosomal peptide synthetase system that programs the 2,2'-BP formation. This likely involves an unusual intramolecular cyclization/rearrangement sequence, and a difference in processing of the sulfhydryl group derived from the same precursor cysteine drives the biosynthetic route toward CAEs or COLs.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China. xudongqu@gmail.com
authors.forename: Xudong
authors.initials: X
authors.lastname: Qu
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Zhuhua
authors.initials: Z
authors.lastname: Wu
authors.forename: Qunfei
authors.initials: Q
authors.lastname: Zhao
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry / Q000378:metabolism*; D003500:Cyclization; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides; D061065:Polyketides; D015082:2,2'-Dipyridyl