Identification of a gene encoding a homocitrate synthase isoenzyme of Saccharomyces cerevisiae

✍ Scribed by Ramos, Fernando; Verhasselt, Peter; Feller, André; Peeters, Pieter; Wach, Achim; Dubois, Evelyne; Volckaert, Guido

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 447 KB
• Volume: 12
• Category: Article
• ISSN: 0749-503X
• DOI: 10.1002/(sici)1097-0061(199610)12:13<1315::aid-yea20>3.0.co;2-q

✦ Synopsis

In Succliarornyces cer-evisiue, most of the L Y S structural genes have been identified except the genes encoding homocitrate synthase and u-aminoadipate aminotransferase. Expression of several L 1's genes responds to an induction mechanism mediated by the product of L YS14 and an intermediate of the pathway, u-aminoadipate semialdehyde (uAASA) as an inducer. This activation is modulated by the presence of lysine in the growth medium leading to an apparent repression. Since the first enzyme of the pathway, homocitrate synthase, is feedback inhibited by lysine, it could be a major element in the control of uAASA supply.

During the sequencing of chromosome IV of S. cerevisiue, the sequence of O R F D1298 showing a significant similarity with the nifT'gene of .4~otobacter vinelundii was reported. Disruption and overexpression of O R F D1298 demonstrate that this gene, named LYSZO. encodes a homocitrate synthase. The disrupted segregants are able to grow on minimal medium and exhibit reduced but significant homocitrate synthase indicating that this activity is catalysed by at least two isoenzymes. We have also shown that the product of LYS20 is responsible for the greater part of the lysine production.

The different isoforms are sensitive to inhibition by lysine but only the expression of LYSZO is strongly repressed by lysine. The N-terminal end of homocitrate synthase isoforin coded by L YS20 contains no typical mitochondrial targeting sequence. suggesting that this enzyme is not located in the mitochondria.