title: Exploring chemical diversity of α-pyrone antibiotics: molecular basis of myxopyronin biosynthesis.
abstract: Myxopyronins and corallopyronins are structurally related α-pyrone antibiotics from myxobacteria. They are thought to represent a highly promising compound class for the development of broad-spectrum antibacterial therapeutic agents, because of their ability to inhibit RNA polymerase through interaction with the "switch region", a recently identified novel drug target. Here we describe the identification and characterization of the myxopyronin biosynthetic pathway from Myxococcus fulvus Mx f50. A detailed comparison with the recently identified corallopyronin biosynthetic pathway revealed the genetic and biochemical basis, thus explaining the observed structural differences between the two natural product families. Directed mutagenesis procedures for M. fulvus Mx f50 were developed to enable functional studies and pathway modifications. Our work provided new insights into myxopyronin biosynthesis and led to the production of a novel and unexpected myxopyronin derivative.
authors: Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Center for Infection Research, Saarland University, Building C2.3, 66123 Saarbrücken (Germany); German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, University Campus Building C2.3, 66123 Saarbrücken (Germany).
authors: Hilda
authors: H
authors: Sucipto
authors: Silke C
authors: SC
authors: Wenzel
authors: Rolf
authors: R
authors: Müller
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D016940:Myxococcus / Q000737:chemistry* / Q000378:metabolism; D011753:Pyrones
chemical_list: D000900:Anti-Bacterial Agents; D007783:Lactones; D011753:Pyrones; C040322:myxopyronin A; C040323:myxopyronin B
keywords: Myxcoccus fulvus; alpha-pyrone antibiotics; biosynthesis; myxobacteria; polyketides