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Mechanism of the stimulatory effect of cyclodextrins on lankacidin-producing Streptomyces
Authors:Hidekazu Sawada  Takashi Suzuki  Shun-ichi Akiyama  Yoshio Nakao
Institution:(1) Microbiology Research Laboratories, Research and Development Division, Takeda Chemical Industries, Ltd., Yodogawa-ku, 532 Osaka, Japan
Abstract:Summary Gel-filtration analysis of a mixture of cyclodextrin (CyD) and lankacidin C showed that beta-CyD had strong, gamma-CyD weak and agr-CyD no affinity for lankacidin C. Lankacidin C production activity, which was assayed by measuring the incorporation of l-methyl-14C-]methionine into the lankacidin molecule, was the greatest with cells grown in the presence of beta-CyD, less with gamma-CyD and the least with agr-CyD. Lankamycin and T-2636M, which are by-products in lankacidin C fermentation, were not included by beta-CyD and their production was not stimulated by beta-CyD. It was apparent that the stimulatory effect of CyD was closely related to the formation of an inclusion complex between CyD and the antibiotic. Lankacidin C biosynthesis was repressed by preincubating cells with lankacidin C, while the repressive effect of lankacidin C was abrogated by the inclusion by beta-CyD. Thus, abrogation of feed-back repression seems to be a main mechanism of the effect of CyD. However, agr-CyD, which had no affinity for lankacidin C, stimulated the production to the least extent and exhibited a complementary effect on the stimulation by beta-CyD or gamma-CyD. agr-CyD also caused a change in cell morphology and cell-surface hydrophobicity. It was assumed that the modification of the cell surface is a secondary mechanism of the effect of CyD.The second report of the stimulatory effect of cyclodextrins on lankacidin fermentationOffprint requests to: H. Sawada
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