NOVEL MICROBIAL INHIBITORS OF ACE - ISOLATION AND CHARACTERIZATION

Two novel microbial ACE- inhibitors BAY o 6997 and BAY q 1313 were det ected in the fermentation broths of streptomyces spec. WS 464 and spec . WS 1065, respectively. Both were isolated and purified by ion exchan ge chromatography as initial steps, and final purification was achieve d by HPLC or additional chromatography of the Cu-chelate (BAY q 1313). Both inhibitors are reversibly inactivated on chelation with CU2+ or Zn2+. Irreversible inactivation occurs on standing in aqueous and acid ic solution or in ammonium hydroxide at room temperature and more rapi dly on heating. In 4 M sodium hydroxide solutions BAY o 6997 is comple tely stable, and BAY q 1313 still remarkably stable even on longer hea ting to 80 degrees C. Thus, BAY o 6997 was alternatively and advantage ously isolated after heating of its solution in 4 M sodium hydroxide t o 37 degrees C for 2 days and subsequent fractional precipitation with ethanol in a relatively pure state. Total hydrolysis yielded His, 2-m ethylamino-4-amino-butyric acid and alpha-keto butyric acid (BAY o 699 7) and pyruvic acid (BAY q 1313) respectively. The unusual stability o f both inhibitors in sodium hydroxide solution on the one hand and the ir instability on heating and storage in aqueous or acidic solutions o n the other hand clearly prove that the constituents are not linked by amide bonds. (C) Munksgaard 1995.