Complestatin, a potent anti-complement substance produced by Streptomyces lavendulae. I. Fermentation, isolation and...

A new potent inhibitor of complement system, named complestatin, was isolated from the mycelium of Streptomyces lavendulae SANK 60477. Complestatin (C61H45N7O15Cl6, MW 1,325) was a peptide compound having two unusual amino acids, D-(-)-4-hydroxyphenylglycine and D-(-)-3,5-dichloro-4-hydroxyphenylglycine. This compound inhibited the hemolysis of sensitized sheep erythrocytes (EA) mediated by guinea pig and human complement 50% at concentrations of 0.4 and 0.7 micrograms/ml, respectively, but did not trypsin and alpha-chymotrypsin activities at 200 micrograms/ml. When complestatin was administered intravenously to the sensitized guinea pigs, it strongly inhibited the systemic anaphylactic shock elicited by the antigen probably by blocking generation of anaphylatoxins (C3a and C5a).