Patent GB-1021721-A (GB)
Title: Improvements in or relating to the production of metabolites by micro-organisms
Inventor: SCHERR GEORGE HARRY
IPC: C12N1/38
Filed: 1962-10-05
Abstract: There is obtained an increased yield of a metabolic product from a culture of a parent micro-organism by subjecting the culture to sufficient concentration of the specific antimetabolite of the metabolite which forms the metabolic product, or precursor thereof, to inhibit growth of the parent micro-organism and forming a culture of those mutant strains which survive by reason of their characteristic enhanced production of the metabolite.  The culture of the parent mico-organism may be subjected to a concentration gradient of the antimetabolite, mutant strains being obtained in the form of isolated colonies of micro-organisms surviving in that part of the gradient where growth of the parent organism has ceased.  Examples are directed to the isolation of (i) a mutant strain of Escherichia coli having a higher yield of nicotinic acid, nicotinamide and/or nicotinuric acid than the parent culture, employing pyridine-3-sulphonic acid as the antimetabolite, (ii) a mutant strain of yeast derived from Saccharomyces microsporus having a higher pyridoxine yield, employing isoniazid as the antimetabolite, and (iii) a mutant strain of Escherichia coli having a higher thiamine yield, employing pyrithiamine hydrogen bromide as the antimetabolite. Where the metabolites of interest are final products not in themselves essential to the organisms from whose culture they are isolated, as in the penicillin production by Penicillium chrysogenum or the fermentation by Rhizopus nigricans to give fumaric acid, the culture is subjected to an optimum concentration of an antimetabolite specific for a precursor to the final product.ALSO:There is obtained an increased yield of a metabolic product from a culture of a parent micro-organism by subjecting the culture to sufficient concentration of the specific antimetabolite of the metabolite which forms the metabolic product, or precursor thereof, to inhibit growth of the parent micro-organism and forming a culture of those mutant strains which survive by reason of their characteristic enhanced production of the metabolite.  The culture of the parent micro-organism may be subjected to a concentration gradient of the antimetabolite, mutant strains being obtained in the form of isolated colonies of micro-organisms surviving in that part of the gradient where growth of the parent organism has ceased.  Examples are directed to the isolation of (i) a mutant strain of Escherichia coli having a higher yield of nicotinic acid, nicotinamide and/or nicotinuric acid than the parent culture, employing pyridine-3-sulphonic acid as the antimetabolite, (ii) a mutant strain of yeast derived from Saccharomyces microsporus having a higher pyridoxine yield, employing isoniazid as the antimetabolite, and (3) a mutant strain of Escherichia coli having a higher thiamine yield, employing pyrithiamine hydrogen bromide as the antimetabolite.  Where the metabolites of interest are final products not in themselves essential to the organisms from whose culture they are isolated, as in the penicillin production by Penicillium chrysogenum or the fermentation by Rhizopus nigricans to give fumaric acid, the culture is subjected to an optimum concentration of antimetabolite specific for a precursor to the final product.