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.
Sawada
H
H
Microbiology Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Suzuki
T
T
Akiyama
S
S
Nakao
Y
Y
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002462:Cell Membrane / Q000187:drug effects; D002850:Chromatography, Gel; D003505:Cyclodextrins / Q000494:pharmacology*; D003912:Dextrins / Q000494:pharmacology*; D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis; D005246:Feedback; D005285:Fermentation; D018942:Macrolides; D013213:Starch / Q000494:pharmacology*; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D003505:Cyclodextrins; D003912:Dextrins; D018942:Macrolides; C008250:lankacidins; D004917:Erythromycin; C100149:kujimycin B; D013213:Starch