Mechanism of action of an antifungal antibiotic, RI-331, (S) 2-amino-4-oxo-5-hydroxypentanoic acid; kinetics of inactivation of homoserine dehydrogenase from Saccharomyces cerevisiae.
An antifungal antibiotic (S) 2-amino-4-oxo-5-hydroxypentanoic acid, inhibited the biosynthesis of the aspartate family of amino acids (methionine, isoleucine and threonine) followed by the inhibition of protein biosynthesis in Saccharomyces cerevisiae. This inhibition was effected by impeding the biosynthesis of their common intermediate precursor, homoserine. The inhibition of biosynthesis of homoserine by the antibiotic was attributable to inactivation of homoserine dehydrogenase [EC 1.1.1.3], which is involved in the conversion of aspartate semialdehyde to homoserine in the metabolic pathway leading to threonine, methionine and isoleucine. Since such enzymic activity is not present in animal cells, the selective antifungal activity of the antibiotic is thus explained.
Institute of Applied Microbiology, University of Tokyo, Japan.
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Yamaki
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Yamaguchi
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Tsuruo
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Yamaguchi
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001222:Aspartate Kinase / Q000187:drug effects; D001223:Aspartate-Semialdehyde Dehydrogenase / Q000187:drug effects; D006715:Homoserine Dehydrogenase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D012441:Saccharomyces cerevisiae / Q000737:chemistry*
D000935:Antifungal Agents; C058222:2-amino-5-hydroxy-4-oxopentanoic acid; D000622:Aminolevulinic Acid; D006715:Homoserine Dehydrogenase; D001223:Aspartate-Semialdehyde Dehydrogenase; D001222:Aspartate Kinase