Zwittermicin A biosynthetic cluster.
The goal of this study was to identify the biosynthetic cluster for zwittermicin A, a novel, broad spectrum, aminopolyol antibiotic produced by Bacillus cereus. The nucleotide sequence of 2.7kb of DNA flanking the zwittermicin A self-resistance gene, zmaR, from B. cereus UW85 revealed three open reading frames (ORFs). Of these ORFs, two had sequence similarity to acyl-CoA dehydrogenases and polyketide synthases, respectively. Insertional inactivation demonstrated that orf2 is necessary for zwittermicin A production and that zmaR is necessary for high-level resistance to zwittermicin A but is not required for zwittermicin A production. Expression of ZmaR was temporally associated with zwittermicin A production. The results suggest that zmaR is part of a cluster of genes that is involved in zwittermicin A biosynthesis, representing the first biosynthetic pathway for an aminopolyol antibiotic.
Stohl
E A
EA
Department of Plant Pathology, University of Wisconsin-Madison, 1630 Linden Drive, Madison, WI 53706, USA.
Milner
J L
JL
Handelsman
J
J
D000123:Acetyltransferases; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001409:Bacillus cereus / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D015153:Blotting, Western; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames / Q000235:genetics / Q000502:physiology; D010455:Peptides; D017422:Sequence Analysis, DNA
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010455:Peptides; C088290:zwittermicin A; D000123:Acetyltransferases; C100968:ZmaR protein, Bacillus