METHIONINE SYNTHESIS IN NEUROSPORA. THE ISOLATION OF CYSTATHIONINE

Abstract

Among artificially produced biochemical mutants of Neurospora, those which have lost the ability to synthesize methionine form the largest class.At the present writing 87 occurrences of the methioninebss character have been observed in this laboratory following treatment of wild type spores with high frequency radiations (1) or mustard gas (2).AIethionineZess mutants differ from wild type Neurospora in that they fail to grow on a medium containing only sugar, inorganic salts, and biotin, but do grow if, in addition to these constituents, methionine is supplied.In many of the mutants failure of methionine synthesis results from a block in the reduction of sulfate, which, except for a trace of biotin, is the sole source of sulfur in the basal medium.These strains can utilize reduced forms of inorganic sulfur for growth, as well as methionine and other organic sulfur compounds.On the other hand, some of the mutants require organically bound sulfur for growth, an indication that in these strains the block in methionine synthesis comes at a later stage than sulfate reduction.Similar classes of methionine-requiring mutants have been reported in the mold Ophiostoma by Fries (3) and in Escherkhia coli by .The present study is concerned with four strains which are unable to carry out certain of the terminal steps in methionine synthesis.Evidence is presented showing that the synthesis proceeds through a series of genecontrolled reactions involving cysteine, cystathionine, and homocysteine as intermediates.Of particular interest is the fact that, as a result of genetic blocking, a precursor of methionine accumulates in cultures of one of the strains.The precursor has been isolated and shown to be chemically and biologically indistinguishable from synthetic L-cystathionine.The results of this investigation were presented at the meeting of the American Society of Biological Chemists in Chicago, May 21, 1947 (7).