title: Molecular basis for chloronium-mediated meroterpene cyclization: cloning, sequencing, and heterologous expression of the napyradiomycin biosynthetic gene cluster.
abstract: Structural inspection of the bacterial meroterpenoid antibiotics belonging to the napyradiomycin family of chlorinated dihydroquinones suggests that the biosynthetic cyclization of their terpenoid subunits is initiated via a chloronium ion. The vanadium-dependent haloperoxidases that catalyze such reactions are distributed in fungi and marine algae and have yet to be characterized from bacteria. The cloning and sequence analysis of the 43-kb napyradiomycin biosynthetic cluster (nap) from Streptomyces aculeolatus NRRL 18422 and from the undescribed marine sediment-derived Streptomyces sp. CNQ-525 revealed 33 open reading frames, three of which putatively encode vanadium-dependent chloroperoxidases. Heterologous expression of the CNQ-525-based nap biosynthetic cluster in Streptomyces albus produced at least seven napyradiomycins, including the new analog 2-deschloro-2-hydroxy-A80915C. These data not only revealed the molecular basis behind the biosynthesis of these novel meroterpenoid natural products but also resulted in the first in vivo verification of vanadium-dependent haloperoxidases.
authors: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, USA.
authors: Jaclyn M
authors: JM
authors: Winter
authors: Michelle C
authors: MC
authors: Moffitt
authors: Emmanuel
authors: E
authors: Zazopoulos
authors: James B
authors: JB
authors: McAlpine
authors: Pieter C
authors: PC
authors: Dorrestein
authors: Bradley S
authors: BS
authors: Moore
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D002384:Catalysis; D003001:Cloning, Molecular; D015870:Gene Expression; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000502:physiology*; D009285:Naphthoquinones / Q000378:metabolism*; D016366:Open Reading Frames / Q000502:physiology; D010544:Peroxidases / Q000096:biosynthesis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D013729:Terpenes / Q000378:metabolism*; D014639:Vanadium / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009285:Naphthoquinones; D013729:Terpenes; D014639:Vanadium; D010544:Peroxidases