Phosphinothricin, a Potent GS Inhibitor

In 1972 the team of Professor Zaehner at Tubingen described a Streptomyces strain producing a novel compound with antibiotic properties. The antibiotic tripeptide produced by Streptomyces viridochromogenes consists of two alanine residues and a novel amino acid that was named phosphinothricin [14] (Fig. 6.3.2). Owing to its structural analogy to glutamate Bayer et al. [14] tested and proved the hypothesis that phosphinothricin acts as an inhibitor of bacterial GS enzyme, whereas the tripeptide phosphinothricyl-alanyl.alanine did not inhibit the isolated GS enzyme. Nevertheless the tripeptide was 1.000-10.000-fold more active in its growth inhibitory effect on different bacteria. The discrepancy is explained by the observation that free phosphinothricin cannot be taken up efficiently by bacteria, whereas the tripeptide is taken up into the bacteria by peptide carriers and, subsequently, the tripeptide is cleaved. 

Independent of the research activities in Germany, a Japanese research team discovered the same tripeptide produced by a Streptomyces isolate from a Japanese soil sample. This isolate was named S. hygroscopicus and the tripeptide was named bialaphos (syn. bilanaphos) [15]. 

In 1984 a third phosphinothricin-produdng microorganism was discovered and described as Kitasatospora phosalacinea (syn. Strq tomyces phosalacineus) which produces phosphinothricyl alanyl-leucine (phosaladne) [16,17]. 

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