Synthesis of Cystathionine and its Control in Salmonella typhimurium

Abstract

CYSTATHIONINE formation in Escherichia coli involves the functioning of two enzymes^1–3. The first enzyme is present in certain cystathionine-requiring auxotrophs such as E. coli strain 7/9 but absent from others (such as strain 2/2) and catalyses the formation of O-succinyl homoserine from homoserine and succinyl coenzyme A. The nature of the product was originally deduced from the chemical and biological properties of the compound³ and this was confirmed by comparison with chemically synthesized O-succinyl homoserine⁴. The second enzyme which is absent from strain 7/9 but present in strain 2/2 forms cystathionine from O-succinyl homoserine plus cysteine². Further evidence for the functioning of O-succinyl homoserine as a methionine precursor in E. coli was afforded by the observation⁵ that strain 7/9 accumulated O-succinyl homoserine when grown with limiting amounts of homocysteine although the addition of methionine abolished the accumulation. Nutritional and genetic investigations with methionine-requiring strains of Salmonella typhimurium⁶ suggested that the biosynthetic pathway might be the same as in E. coli. Two other observations support this view. First, organisms of S. typhimurium strain B23, a cystathionine-requiring mutant, accumulate O-succinyl homoserine in the culture fluid⁵, while a genetically dissimilar cystathionine-requiring strain (strain A15) shows no accumulation. Secondly, extracts from S. typhimurium strain A form cystathionine from O-succinyl homoserine plus cysteine⁷. These data supported the view that cystathionine and O-succinyl homoserine are methionine precursors in S. typhimurium and, as the accumulation of O-succinyl homoserine by strain B23 (like that with E. coli strain 7/9) was prevented by methionine⁵, it appeared that control of the biosynthetic pathway might be similar to that in E. coli². The present work shows that S. typhimurium contains both enzymes of cystathionine formation and that enzymatic repression and feed-back inhibition occur.