Examples of useful substances synthesized from PRPP on the microbial metabolic pathway include nucleic acid-related substances such as purine nucleotides, pyrimidine nucleotides, purine nucleosides, pyrimidine nucleosides, purine bases, pyrimidine bases and flavin nucleotides, as well as L-histidine and riboflavin.
These nucleic acid related substances, L-histidine, riboflavin and the like have been produced industrially by a fermentation method or by a combination of a fermentation method with a synthetic method. See Applied Microbiology, edited by Shoichi Takao et al., Buneido Shuppan (1996); Amino Acid Fermentation, edited by Hiroshi Aida et al., Gakkai Shuppan Center (1986); JP-A-6-225776 ("JP-A" as used herein means an "Japanese Published Unexamined Patent Application").
In microorganisms, PRPP is biologically synthesized by a PRPP synthetase from ribose 5-phosphate which is an intermediate in the pentose phosphate pathway.
As the biosynthetic pathways of ribose 5-phosphate, an oxidative pentose phosphate pathway via glucose 6-phosphate dehydrogenase is known, and it is expected that a non-oxidative pentose phosphate pathway is also involved in its biosynthesis because all of the enzymes on the non-oxidative pentose phosphate pathway via transketolase reaction are reversible (see FIG. 1).
It has been determined by a study of the metabolism of labeled glucose that both of these pathways are concerned in the biosynthesis of ribose 5-phosphate in Escherichia coli, see Biochemistry, 12, 10, 1969 (1973). Also, it has been shown by genetic studies that ribose 5-phosphate is provided by the non-oxidative pentose phosphate pathway via transketolase reaction, because glucose 6-phosphate dehydrogenase-deficient strains of Escherichia coli and Corynebacterium glutamicum do not show ribose auxotrophy, see D. G. Fraenkel and R. T. Vinopal, Ann. Rev. Microbiol., 27, 69-100 (1973); E. D. Ihnen and A. L. Demain, J. Bacteriol., 98, 1151-1158 (1969).
This information suggests that increase in the activity of transketolase enables increased supply of ribose 5-phosphate and PRPP from the non-oxidative pathway and therefore the amount of substances biologically synthesized from PRPP is increased.
In addition, it has been reported that a transketolase activity-deficient strain in inosine-producing strains belonging to the genus Bacillus such as Bacillus subtilis accumulates a considerable amount of ribose in the culture medium so that the yield of purine nucleotide production is reduced, see K. Sasajima and M. Yoneda, Biotechnol. Genet. Eng. Rev., 2, 175-213 (1984).
This information also suggests that the activity of transketolase is necessary for the production of substances biologically synthesized from PRPP. However, to date, with respect to all microorganisms, it has not been known that the production yield of metabilites to be biologically synthesized via PRPP is improved by having transketolase activity lost or reduced.
Since demands have been increasing for metabolites biologically synthesized via PRPP, particularly nucleic acid-related substances, L-histidine and riboflavin and the like, the development of an industrially advantageous method for their production is strongly desired.
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