Patent GB-1071935-A (GB)
Title: Synthesis of amino acids
IPC: C12P13/04
Filed: 1965-04-07
Abstract: Amino-acids are produced microbially by (a) incubating an amino-acid-producing hydrocarbon-utilizing micro-organism in the presence of oxygen and a hydrocarbon as the sole source of carbon in a nutrient medium containing an inhibitory amount of a growth inhibitor which is a chemically similar derivative of the required amino-acid, so as to inhibit the growth of the organism except for at least one mutant which is resistant to the inhibitory effect; (b) isolating the resistant mutant and growing it in the presence of oxygen and the hydrocarbon in the absence of the inhibitor; (c) harvesting the mutant cells; (d) forming a nutrient medium which includes a hydrocarbon as the sole source of carbon; and (e) incubating the harvested cells in the medium in the presence of oxygen. Suitable organisms are found among Pseudomonas, Escherichia, Bacillus, Staphylococcus, Salmonella, Flavobacterium and Sarcina, e.g. among P. aeruginosa, P. fluorescens, P. pyocyanea, E. coli, B. aureus, B. acidi, B. subtilis, B. urici, B. cereus, B. coagulans, B. mycoides, B. circulans, B. megaterium, Staph. albus, Staph. aureus (Micrococcus pyogenes var. aureus), S. typhimurium, Flavobacterium aquiatile, Sarcina alba, Sarcina luteam and Leuconostoc mesenteroides. Suitable hydrocarbons and media are listed.  The following amino-acid products are specified (suitable inhibitors given in brackets): phenylalanine (o-fluorophenylalanine, thienylalanine, p-aminophenylalanine, b -phenylserine, b -furylalanine); tyrosine (p-fluorophenylalanine, 3-fluorotyrosine); serine (serine methyl ester); valine (norvaline, a -amino-b -chlorobutyric acid, a -hydrazinoisovaleric acid); methionine (ethionine, norleucine); leucine (methallylglycine, a -hydrozinoisocaproic acid, b -cyclopentanealanine); lysine (o -methyllysine); tryptophan (6 - fluorotryptophan, 5 - fluorotryptophan, 6-, 5- or 4-methyltryptophan, azatryptophan); arginine (homoarginine); and isoleucine (cyclohexaneglycine).  Other inhibitors are also specified.  In some cases another amino-acid may be obtained in addition to the listed one.ALSO:A mutant strain of a hydrocarbon-utilizing micro-organism for the production of amino-acids (see Division C2) is prepared by (a) incubating the organism in the presence of oxygen and of a hydrocarbon as the sole source of carbon in a nutrient medium containing an inhibitory amount of a growth inhibitor which is a chemically similar derivative of the required amino-acid, so as to inhibit the growth of the organism except for at least one mutant which is resistant to the inhibitory effect; (b) isolating the resistant mutant and growing it in the presence of oxygen and the hydrocarbon and in the absence of the inhibitor; and (c) harvesting the mutant cells.  Suitable organisms are found among Pseudomonas, Escherichia, Bacillus, Staphylococcus, Salmonella, Flavobacterium, and Sarcina, e.g. among P. aeruginosa, P. fluorescens, P. pyocyanea, E. coli, B. aureus, B. acidi, B. subtilis, B. urici, B. cereus, B. coagulans, B. mycoides, B. circulans, B. megaterium, Staph. albus, Staph. aureus (Micrococcus pyogenes var. aureus), S. typhimurium, Flavobacterium aquatile, Sarcina alba, Sarcina luteam, and Leuconostoc mesenteroides.  Many inhibitors and the corresponding amino-acids obtained by culturing the mutant strains are listed (see Division C2).