Studies on the Biosynthesis of Tabtoxin (Wildfire Toxin). Origin of the Carbonyl C-Atom of the β-Lactam Moiety from the C1-Pool

Re-isolation of Pseudomonas tabaci strain NCPPB 2730 from its host, the tobacco plant, led to an activation of the bacteria in order to produce the β-lactam dipeptide tabtoxin (Wildfire toxin, 1 ). Incorporation of several ¹⁴C-labelled amino acids as well as L -methyl-¹³C]methionine, L -1,2-¹³C₂]- and L -3,4-¹³C₂]aspartate, rac -1,2-¹³C₂]glycerol, and 1,2-¹³C₂]acetate into isotabtoxion ( 2 ) demonstrated that the building blocks of tabtoxin ( 1 ) are L -threonine, L -aspartate, the Me group of L -methionine and a C₂-unit derived from the C₃-pool (Fig. 3). The Me group of L -methionine provides the carbonyl C-atom of the β-lactam moiety. These findings represent a novel pathway in β-lactam biosynthesis. Mechanistic aspects with respect to the β-lactam ring formation are discussed. A biradical 16 is proposed as an intermediate during the cyclization of a N-formyl-α-amino ketone 15 .