Characterization of Enzymes Catalyzing the Initial Steps of the β-Lactam Tabtoxin Biosynthesis

Abstract

Tabtoxin is a β-lactam ring-containing phytotoxin produced by a plant pathogenic Pseudomonas species. Here, we describe the early stages of tabtoxin biosynthesis, involving a C-methylation reaction catalyzed by the S-adenosyl-l-methionine-dependent methyltransferase TblA as the initial step for the β-lactam construction. Gene deletion and in vitro biochemical assays demonstrated that the Gcn5-related N-acetyltransferase domain of TblD catalyzes the acetylation of the α-amino group of 5-methyl-l-lysine. This establishment of the early reaction steps lays the foundation for characterizing unique β-lactam biosynthesis.

β-Lactams from the Ocean

“…Its Gram-positive and Gram-negative antibacterial activity is the result of an ATP-dependent inhibition of glutamine synthetase, and not from inhibition of bacterial cell-wall synthesis. The mechanism of this inhibition, as studied with the related β-lactam structure tabtoxinine-β-lactam (“tobacco wildfire toxin”) biosynthesized by terrestrial Pseudomonas bacteria [ 106 , 107 ], does not involve the opening of its β-lactam ring [ 108 , 109 ]. Chartelline B was isolated in 1987 (as one of several related structures) from the marine bryozoan Chartella papyracea .…”