Biochemical Mechanism of the Effect of Barbital on Rifamycin B Biosynthesis by Amycolatopsis mediterranei (M18 Strain)

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It is well known that 5,5-diethylbarbituric acid (barbital) in the culture medium can stimulate the production of rifamycin B by Amycolatopsis mediterranei, particularly in industrial processes. However, the mechanism by which barbital exerts this effect is unknown. Results in this work show that the barbital effect is only evident under low aeration conditions (50-ml microfermentors with 7 ml of medium, 0.08 l/h air flow). Under these conditions, cultures with barbital showed similar CO_2 production (in relation to a control without barbital), but higher oxygen uptake indicated that the extra O_2 consumed was used in the increased rifamycin biosynthesis. Moreover, using a resting cell system where no antibiotic is produced, it was possible to show that barbital inhibits the respiratory chain, since O_2 uptake decreased by 30%. Finally, we present biochemical results that suggest that a cytochrome P450-type monoxygenase, which can use atmospheric oxygen, is induced by barbital in an industrial-type strain of A. mediterranei.
社団法人日本生物工学会の論文
2003-03-25