Genetic and Regulatory Aspects of Methionine Biosynthesis in Saccharomyces cerevisiae

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Methionine biosynthesis and regulation of four enzymatic steps involved in this pathway were studied in Saccharomyces cerevisiae, in relation to genes concerned with resistance to ethionine (eth1 and eth2). Data presented in this paper and others favor a scheme which excludes cystathionine as an obligatory intermediate. Kinetic data are presented for homocysteine synthetase [Km(O-acetyl-l-homoserine) = 7 × 10−3m; Ki (l-methionine) = 1.9 × 10−3m]. Enzymes catalyzing steps 3, 4, 5, and 9 were repressible by methionine. Enzyme 4 (homoserine-O-transacetylase) and enzyme 9 (homocysteine synthetase) were simultaneously derepressed in strains carrying the mutant allele eth2r. Studies on diploid strains confirmed the dominance of the eth2s allele over eth2r. Regulation of enzyme 3 (homoserine dehydrogenase) and enzyme 5 (adenosine triphosphate sulfurylase) is not modified by the allele eth2r. The other gene eth1 did not appear to participate in regulation of these four steps. Gene enzyme relationship was determined for three of the four steps studied (steps 3, 4, and 9). The structural genes concerned with the steps which are under the control of eth2 (met8: enzyme 9 and meta: enzyme 4) segregate independently, and are unlinked to eth2. These results are compatible with the idea that the gene eth2 is responsible for the synthesis of a pleiotropic methionine repressor and suggest the existence of at least two different methionine repressors in S. cerevisiae. Implications of these findings in general regulatory mechanisms have been discussed.

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