Production of 12-Ketochenodeoxycholic Acid by Two-stage Continuous Fermentation with pH Control at Different Levels

概要

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The production conditions of 12-ketochenodeoxycholic acid from dehydrocholic acid by Lactobacillus xylosus DC1115 were studied. The optimal conditions for growth were found to be pH 7 to 7.5 and 37℃. In single-stage continuous fermentation, the intermediate 7,12-diketolithocholic acid was accumulated in about 80 % yield from the substrate at any dilution rate at pH 7,and the maximum yield of product was 22 % at the dilution rate of 0.13/hr. Rate analysis of individual reaction steps revealed that the reverse eraction of product formation was appreciable, and led us to postulate the following scheme for the biotransformation : dehydrocholic acid ⟶^^I 7,12-diketolithocholic acid [numerical formula] 12-ketochenodeoxycholic acid.Rate I was much higher than rates II and II', and rate II' was higher than rate II at pH 7 with cells grown at any dilution rate. Rates I and II' were maximum at pH 7 to 8 and pH 8,respectively, while rate II increased with devreasing pH and at acidic pH it exceede rate II'. In two-stage continuous fermentation, the pH in the first stage was controlled at 7.2 with a dilution rate of 0.2/hr, while in the second stage production was maximized at pH 5.5 with a dilution rate of 0.1/hr, The maximum production of 12-ketochenodeoxycholic acid was raised to 55% yield in the two-stage fermentation from 22% in the single-stage fermentation.
社団法人日本生物工学会の論文
1981-02-25