Mechanism of the stimulatory effect of cyclodextrins on lankacidin-producing Streptomyces.

Gel-filtration analysis of a mixture of cyclodextrin (CyD) and lankacidin C showed that beta-CyD had strong, gamma-CyD weak and alpha-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 alpha-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, alpha-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, alpha-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.