Characterization of the Complete Zwittermicin A Biosynthesis Gene Cluster fromBacillus cereus

Abstract

Bacillus cereus UW85 produces the linear aminopolyol antibiotic zwittermicin A (ZmA). This antibiotic has diverse biological activities, such as suppression of disease in plants caused by protists, inhibition of fungal and bacterial growth, and amplification of the insecticidal activity of the toxin protein from Bacillus thuringiensis. ZmA has an unusual chemical structure that includes a D amino acid and ethanolamine and glycolyl moieties, as well as having an unusual terminal amide that is generated from the modification of the nonproteinogenic amino acid ␤-ureidoalanine. The diverse biological activities and unusual structure of ZmA have stimulated our efforts to understand how this antibiotic is biosynthesized. Here, we present the identification of the complete ZmA biosynthesis gene cluster from B. cereus UW85. A nearly identical gene cluster is identified on a plasmid from B. cereus AH1134, and we show that this strain is also capable of producing ZmA. Bioinformatics and biochemical analyses of the ZmA biosynthesis enzymes strongly suggest that ZmA is initially biosynthesized as part of a larger metabolite that is processed twice, resulting in the formation of ZmA and two additional metabolites. Additionally, we propose that the biosynthesis gene cluster for the production of the amino sugar kanosamine is contained within the ZmA biosynthesis gene cluster in B. cereus UW85.

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

“…67 They encode an oxidoreductase (KabC), a transaminase (KabA) and a hydrolase (KabB). KabC and KabB correspond to rifL and rifM, respectively, in the rif cluster, but there is no obvious candidate for the aminotransferase in the cluster.…”

Detection and Tracking of a Novel Genetically Tagged Biological Simulant in the Environment

“…In particular, loss of pXO1 from B. anthracis strains is associated with numerous phenotypic changes, including changes to sporulation kinetics, nutritional requirements, and phage sensitivity (42). Our strain also had lost a suite of genes involved in the biosynthesis of zwittermicin, a biologically active compound that, among other activities, potentiates the activity of crystal toxins in insect hosts (6,27). The loss of this gene cluster containing large polyketide synthase modules is reminiscent of the early loss of surfactin biosynthesis during the domestication of B. subtilis and B. atrophaeus subsp.…”

“…kurstaki in test sites is complicated by the fact that both organisms occur naturally in the environment (18; see also the excellent review of environmental B. thuringiensis subsp. kurstaki prevalence by Van Cuyk et al [27]). B. thuringiensis subsp.…”

“…globigii and B. thuringiensis subsp. kurstaki make specific identification of newly disseminated isolates difficult (16,27). Furthermore, once disseminated, spores can persist in the environment for years or even decades (22,26), complicating analysis of subsequent field release tests.…”

Formulation of a novel antagonistic bacterium based biopesticide using microencapsulated techniques in fungal disease control

“…B. cereus DGA34 naturally produces the antibiotic zwittermicin A, an effective antibiotic against a wide range of bacteria and fungi to reduce symptoms of damping-off disease and root rot (Handelsman, Jacobson & Stabb, 1998). B. cereus UW85, generating two antibiotics (zwittermicin A and antibiotic B) (Silo-Suh, Lethbridge, Raffle, He, Clardy, & Handelsman, 1994), has been proven to be a dependable biocontrol agent, which protects cucumber fruits from rot caused by Pythium aphanidermatum, alfalfa seedlings from dampening off due to Phytophthora medicaginis, tobacco seedlings from Phytophthora nicotianae and peanuts from Sclerotinia minor (Silo-Suh et al, 1994). However, only few B. cereus strains have current United States patents as biocontrol agents for crop diseases.…”