COMPARATIVE-STUDIES OF SUIDATRESTIN, A SPECIFIC INHIBITOR OF TREHALASES

Suidatrestin, isolated from a Streptomyces strain, was characterized a s a new trehalase inhibitor. Its inhibitory potential was 7 to 50-fold higher than that of validamycin when tested against insect, fungal an d mammalian trehalases. The kinetic properties of suidatrestin were st udied in vitro with trehalases from flight muscle mitochondria of the fly, Protophormia terraenovae, from larval midgut of the moth, Spodopt era littoralis, and from porcine kidney, as well as with maltase from yeast. Suidatrestin was inactive on maltase but inhibited all trehalas es with IC50 values of 0.08-0.1 mu M; Ki values ranged from 0.02 to 0. 05 mu M. The very low K-i/K-m ratios (3.9 x 10(-6)-4.9 x 10(-6)) indic ated excellent in vitro inhibitory action of suidatrestin. When inject ed into larvae of S. littoralis, suidatrestin required high and repeti tive doses which lead to reversible inhibition of larval growth only. Consecutive omission of the inhibitor even stimulated weight increase above that of controls. Significant mortality was achieved at a rather high dose only. Injection of a growth-inhibiting dose of suidatrestin did not change hemolymph osmolality as a measure of sugar concentrati on. The discrepancy between in vitro and in vivo potency of suidatrest in may be understood once its chemical structure is fully known. (C) 1 998 Elsevier Science Inc. All rights reserved.