ALAPHOSPHALIN ( L -ALANYL- L -1-AMINOETHYLPHOSPHONIC ACID) INHIBITS AC- CoA -DEPENDENT PATHWAYS OF MICROMYCETES BIOSYNTHESIS
KHOMUTOV R. M., KHURS E. N., BIRYUKOV A. I., ZHUKOV YU. N., DZHAVAHIA V. G., VOINOVA T. M., ERMOLINSKY B. S.
V. A. Engelhardt Institute of Molecular Biology, Academy of Sciences of the USSR, Moscow; * All-Union Research Institute of Phytopathology , Moscow Region
Abstract: Dipeptide alaphosphalin (L-alanyl-L-1-aminoethylphosphonic acid, Ala-Ala-P) is known to act by interfering with the biosynthesis of bacterial cell walls similarly to penicilline, cycloserine and some other antibiotics. We found Ala-Ala-P and related compounds to affect other metabolically important processes both in bacteria and in other organisms. We suppose that they penetrate into cells by means of peptide permease system, then phospho-containing dipeptide is hydrolysed by aminopeplidase, yielding L-1-aminoethylphosphonic acid (Ala-P). The last compound is transaminated to give the phosphonate analogue of pyruvate (Ac-P), acetylphosphonate, which is a potent inhibitor of pyruvate dehydrogenase. The inhibition of the CoASAc synthesis may account for the antimicrobial action of Ala-Ala-P. Similar data were obtained with 1-aminoethyl-phosphonic acid (Ala-Pu) and dipeptide Ala-Ala-PH.
Russian Journal of Bioorganic Chemistry 1990, 16 (2):275-279