The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
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
HIROSHI YAMAKIMAKI YAMAGUCHITAKASHI TSURUOHIDEYO YAMAGUCHI
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1992 Volume 45 Issue 5 Pages 750-755

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Abstract

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.

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