title: Structures and comparative characterization of biosynthetic gene clusters for cyanosporasides, enediyne-derived natural products from marine actinomycetes.
abstract: Cyanosporasides are marine bacterial natural products containing a chlorinated cyclopenta[a]indene core of suspected enediyne polyketide biosynthetic origin. Herein, we report the isolation and characterization of novel cyanosporasides C-F (3-6) from the marine actinomycetes Salinispora pacifica CNS-143 and Streptomyces sp. CNT-179, highlighted by the unprecedented C-2' N-acetylcysteamine functionalized hexose group of 6. Cloning, sequencing, and mutagenesis of homologous ~50 kb cyanosporaside biosynthetic gene clusters from both bacteria afforded the first genetic evidence supporting cyanosporaside's enediyne, and thereby p-benzyne biradical, biosynthetic origin and revealed the molecular basis for nitrile and glycosyl functionalization. This study provides new opportunities for bioengineering of enediyne derivatives and expands the structural diversity afforded by enediyne gene clusters.
authors: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, USA.
authors: Amy L
authors: AL
authors: Lane
authors: Sang-Jip
authors: SJ
authors: Nam
authors: Takashi
authors: T
authors: Fukuda
authors: Kazuya
authors: K
authors: Yamanaka
authors: Christopher A
authors: CA
authors: Kauffman
authors: Paul R
authors: PR
authors: Jensen
authors: William
authors: W
authors: Fenical
authors: Bradley S
authors: BS
authors: Moore
mesh_terms: D039903:Actinobacteria / Q000737:chemistry* / Q000235:genetics*; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D053281:Enediynes / Q000737:chemistry; D005798:Genes, Bacterial; D006027:Glycosides / Q000737:chemistry* / Q000235:genetics*; D007192:Indenes / Q000737:chemistry*; D005810:Multigene Family; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics
chemical_list: D001688:Biological Products; D053281:Enediynes; D006027:Glycosides; D007192:Indenes; C514853:cyanosporaside A; C514854:cyanosporaside B