A tabtoxinine-related metabolite from Pseudomonas syringae pv. tabaci

The Journal of Organic Chemistry
1991.0

Abstract

Many pathogenic bacteria excrete metabolites that are toxic to their hosts and play an important role in the virulence mechanisms underlying the corresponding diseases. An understanding of the biosynthesis of these compounds and the self-protection mechanisms evolved by the producing bacteria may aid in the development of new and better forms of treatment of bacterial infections. The biosynthetic pathways are typically revealed through studies on a set of mutants deficient in toxin production/excretion where, ideally, each mutant is altered at only a single genetic locus. The best way of obtaining such mutants is through gene disruption by transposon mutagenesis, with transposons (Tn# (# stands for n = 1,2,3,...)) being DNA sequences that can insert themselves somewhat randomly into other DNA sequences, but once resident in a cell generally prevent further entry of identical transposons. These transposons carry one or more antibiotic resistance genes, which allow for the selection of mutated bacteria on antibiotic-containing media, and the genes interrupted by a given transposon can be identified via hybridization with a radioactive probe. However, identification of the functions of the affected genes requires the identification/structural elucidation of metabolites that accumulate due to the biosynthetic blocks that were introduced. The tools of organic chemistry and molecular biology thus become very much complementary. We are using such a combined approach to unravel the virulence mechanisms of Pseudomonas syringae pv. tabaci, the cause of wildfire disease in tobacco, and report here on the structural elucidation of Nε-acetyl-5-hydroxy-5-(hydroxymethyl)lysine, 1, from a Tn5-generated Tox⁻ mutant. 1 is chemically closely related to tabtoxinine, 2, which itself is obtained from tabtoxinine β-lactam, 3, by acid hydrolysis. 3 has been identified as the actual wildfire toxin; however, P. syringae pv. tabaci excretes it as a nontoxic dipeptide with serine or threonine, the so-called tabtoxin, from which 3 is liberated in planta by peptidases. As judged by our chromatographic assays, 20 Tox⁺ isolates of P. syringae pv. tabaci from diverse tobacco growing areas around the world produce 1 as a minor component (at 5% of the amount of 3) whereas nine naturally occurring Tox⁻ strains do not. 1 therefore is likely to be an intermediate in the biosynthetic pathway of 3 rather than a shunt metabolite thereof.

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