New Amino Acids from Streptomyces*

Biochemistry
1967.0

Abstract

Two new amino acids, 2-amino-3-dimethylaminopropionic acid and 2-amino-4,4-dichlorobutyric acid, have been isolated from fermentations of Streptomyces species. Both compounds, which have the L configuration, have been found to inhibit the growth of several bacteria grown in synthetic media. Isolation of these compounds and work supporting the proposed structures for these antimetabolites are discussed. 2-Amino-3-dimethylaminopropionic acid has been isolated from fermentations of Streptomyces neocaliberis var. neocaliberis while the other, 2-amino-4,4-dichlorobutyric acid is produced by Streptomyces armentosus var. armentosus. The present paper describes the production, isolation, chemical properties, and the structure of these compounds. Some of the biological properties are presented in this paper. However detailed studies of the behavior of both compounds will be presented in subsequent communications. The name linatine (I) was assigned to a vitamin B6 antagonist isolated from linseed meal. Compound I inhibited the growth of chickens and Azotobacter vinelandii O, the assay organism. An LD50 of 2-mg per week-old chick was counteracted by simultaneous injection of 1 mg of pyridoxine. Acid hydrolysis of I yielded L-glutamic acid and a toxic substance (II), LD50 = 0.5 mg in 1-week-old chicks, which was characterized as 1-amino-α-proline, mp 155° dec, [α]D²⁵ + 113° (c 2, 0.5 M HCl); 3-nitrobenzylidene derivative, mp 123°; 2-hydroxy-5-nitrobenzylidene derivative, mp 136°, [α]D²⁵ +151° (c 0.35, ethanol). Compound II was prepared in 60% yield by reduction of 1-nitroso-D-proline with zinc dust in acetic acid. N-Carbobenzyloxyglutamic acid γ-hydrazide was converted to the azide and treated with the benzyl ester of II. Hydrogenolysis of the product yielded 1-[(N-γ-L-glutamyl)amino]-proline that was identical with I, [α]D²⁵ +46.4° (c 2.75, water). 1-[(N-γ-Glutamyl)amino]-proline prepared in the same manner showed [α]D²⁵ - 34.6° (c 2, water). Both I and the diastereoisomer were equally toxic to chicks, but I was about 50 times more toxic toward A. vinelandii O.

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