Metabolic relationship between cystathionine and methionine in Neurospora.

The precursor relationship of cystathionine in the biosynthesis of methionine by Neurospora crassa was first indicated by Horowitz (1947). Isotope competition studies with N. crassa yielded evidence that the sulfur of cystathionine can supply a large portion of the sulfur needed for growth (Roberts et al., 1955). Isolation of the cystathionine-cleaving enzymes and their respective reaction products from different N. crassa methionineless mutants further indicated the validity of the precursor role of cystathionine and supported the concept of transsulfuration in N. crassa (Fischer, 1957). Cystathionine has been designated as a biosynthetic intermediate in methionine formation in both mammals and microorganisms. Evidence for and against its biological significance has been presented in the literature. The investigation reported here was initiated to evaluate the position of cystathionine in methionine biosynthesis by utilizing biochemical mutants of N. crassa, blocked in the pathway of methionine biosynthesis, in isotopic conversion studies. Primary objectives have been: (a) to determine the source of the carbon chains and sulfur of cystathionine and, (b) to find whether radioactive cystathionine contributes to the carbon chain or sulfur of methionine. The first part has been studied for several combinations of time and methionine substrate concentration.