title: Function of the loading module in CorI and of the O-methyltransferase CorH in vinyl carbamate biosynthesis of the antibiotic corallopyronin A.
abstract: Corallopyronin A is a promising in vivo active antibiotic, currently undergoing preclinical evaluation. This myxobacterial compound interferes with a newly identified drug target site, i.e., the switch region of the bacterial DNA-dependent RNA-polymerase (RNAP). Since this target site differs from that of known RNAP inhibitors such as the rifamycins, corallopyronin A shows no cross-resistance with other antibacterial agents. Corallopyronin A is a polyketide synthase- and nonribosomal peptide synthetase-derived molecule whose structure and biosynthesis is distinguished by several peculiarities, such as the unusual vinyl carbamate functionality whose formation involves carbonic acid as an unprecedented C1-starter unit. Using in vitro experiments the nature of this starter molecule was revealed to be the methyl ester of carbonic acid. Biochemical investigations showed that methylation of carbonic acid is performed by the O-methyltransferase CorH. These experiments shed light on the biosynthesis of the Eastern chain of α-pyrone antibiotics such as corallopyronin A.
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
authors.forename: Till F
authors.initials: TF
authors.lastname: Schäberle
authors.forename: Mahsa
authors.initials: M
authors.lastname: Mir Mohseni
authors.forename: Friederike
authors.initials: F
authors.lastname: Lohr
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmitz
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
mesh_terms: D020816:Amino Acid Motifs; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002255:Carbonic Acid / Q000737:chemistry / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D004952:Esters; D015870:Gene Expression; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009231:Myxococcales / Q000737:chemistry / Q000201:enzymology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014520:Urethane / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004952:Esters; D007783:Lactones; D011994:Recombinant Proteins; C532894:corallopyronin A; D014520:Urethane; D002255:Carbonic Acid; C017963:vinyl carbamate; D008780:Methyltransferases; D012321:DNA-Directed RNA Polymerases