Tendamistat (HOE 467), a tight-binding α-amylase inhibitor from Streptomyces tendae 4158: isolation, biochemical properties

Culture fluids of Streptomyces tendae 4158 (ATCC 31210) contain a new kind of polypeptide alpha-amylase inhibitor, tendamistat (HOE 467). Several methods of isolating this inhibitor are described, including two rapid crystallisation methods, which produce homogeneous material. A characteristic of tendamistat is its tight-binding, pH-independent inhibition kinetics and the specific inhibition of the mammalian alpha-amylase form a stoichiometric 1:1 complex, which cannot be separated into its individual components by sodium dodecyl sulphate or molecular sieve chromatography. Studies of the mode of action reveal that the alpha-amylase-inhibiting activity is linked to the intact disulphide bridges of the inhibitor. It is assumed that the multipoint protein-protein bond exists between the enzyme and tendamistat. It is shown that extracellular tendamistat inhibits amylase formed by streptomyces. We therefore assume a regulatory function in the microorganism. By-products of tendamistat, which possess similar enzyme-inhibiting properties, are also described.