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Biosynthesis, regulation and role of AMB

Description | Bibliography
 

Description

AMB was discovered by the Hofmann LaRoche group during a search for new antibiotics and shown to act as a growth inhibitor of Escherichia coli and Bacillus spp. Subsequent studies demonstrated an inhibitory effect of AMB on cultured Walker carcinosarcoma cells and we recently showed that AMB can also inhibit growth and induce encystment in Acanthamoeba castellanii.
AMB is the first amino acid analog discovered to possess an enol ether group and as such belongs to the family of naturally occurring γ–substituted vinylglycines which include aminoethoxyvinylglycine, dimethyliminooxyvinylglycine and guanidinooxyvinylglycine from Streptomyces spp, rhizobitoxine from Bradyrhizobium japonicum and Pseudomonas andropogonis, as well as 4-formylaminooxyvinylglycine, isolated recently from Pseudomonas fluorescens WH6. Being an inhibitor of pyridoxal phosphate-dependent enzymes, AMB has multiple targets in bacteria, animals and plants and as such could potentially act as a P. aeruginosa virulence factor.
We identified a five-gene cluster that is necessary for AMB formation. These genes encode a putative LysE-type transporter (AmbA) suspected to be involved in AMB export, two peptide synthetases (AmbB and AmbE), and two putative α-ketoglutarate-dependent non-heme iron oxygenases of the TauD family (AmbC and AmbD). We thus predict that AMB is synthesized by a thiotemplate mechanism to form a larger precursor peptide which may be hydroxylated during the assembly. The aim of our current work is to elucidate the AMB biosynthesis pathway and to understand the regulation of the genes involved.

 

Bibliography

X. Lee X, A. Fox A, J. Sufrin, H. Henry, P. Majcherczyk, D. Haas & C. Reimmann. 2010. Identification of the biosynthetic gene cluster for the Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid. J. Bacteriol. 192, 4251-4255.

X. Lee, C. Reimmann, G. Greub, J. Sufrin & A. Croxatto. 2011. The Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth and induces encystment in Acanthamoeba castellanii. Microbes Infect. / Institut Pasteur.

 


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