GROWTH INHIBITION OF NEUROSPORA BY CANAVANINE, AND ITS REVERSAL

Abstract

Canavanine, an amino acid from jack beans, was discovered by Kitagawa and coworkers in 1929 (1, 2).The substance is not combined in the proteins of the seed, but occurs in the free state, and makes up 2.5 per cent of the dry weight of jack beans (3).In a series of papers available to the authors for the most part in abstract only, the Japanese workers have reported extensive investigations into the chemistry and physiology of the substance.The structure of canavanine was established by Gulland and Morris (4) and by Kitagawa and Takani (5) as NH2.C( :NH).NH.O.-CH2.CH2.CHNH2.COOH.Natural canavanine is of the I, configuration (6).Canavanine is split by a liver enzyme to yield urea and canaline, NH*.-0 + CH:!.CH2.CHNHz .COOH (3).More recent evidence has indicated that the canavanine-splitting enzyme may be identical with arginase (7).It has been claimed by Ogawa ((8) and elsewhere) that canavanine is essential for young rats.The amino acid is non-toxic to mice, but produces symptoms of intoxication when injected into dogs in a dose of 200 to 400 mg.per kilo of body weight (9).In experiments designed to test the effectiveness of canavanine in supporting the growth of certain amino acid-requiring mutants of Neurospora we found instead that the substance exerts a strong inhibitory effect on the growth of the mold.Further investigation has revealed a number of interesting aspects of this phenomenon, among which are the high degree of toxicity of the substance for the mold, the complete reversibility of the inhibition under certain conditions, and the existence of a genetic factor determining sensitivity or tolerance. Materials and MethodsThe strains of mold used in this study are lA, 4A, and 25a.All are wild type strains of Neurospora crassa, derived originally from single