Fluostatins A and B, New Inhibitors of Dipeptidyl Peptidase III, Produced by Streptomyces sp. TA-3391

I. Taxonomy of Producing Strain, Production, Isolation, Physico-chemical Properties and Biological Properties

Abstract

New inhibitors of dipeptidyl peptidaseIII (EC 3.4.14.4) from human placenta, designated as fluostatins A and B, were discovered in the fermentation broth of a strain isolated in our institute. The strain has been identified as Streptomyces sp. TA-3391 on the basis of taxonomic studies. Fluostatins A and B were purified by Diaion HP-20 chromatography, ethyl acetate extraction, silica gel chromatography and reverse phase preparative HPLC.
With the synthetic substrate, arginyl-arginine-2-naphthylamide, the IC₅₀ values of fluostatins A and B were 0.44 and 24.0 μg/ml, respectively. Fluostatins A and B were slightly inhibitory against other dipeptidyl peptidases. Fluostatin A showed mixed-type (competitive and noncompeptitive) inhibition with human leucine-enkephalin as a substrate, and the inhibition constant (Ki) was 14.2 μM.