Signal Transduction Inhibitors, Hibarimicins A, B, C, D and G Produced by Microbispora

I. Taxonomy, Fermentation, Isolation and Physico-chemical and Biological Properties

Abstract

Strain TP-A0121 which produces a complex of novel tyrosine kinase inhibitors designated hibarimicins A, B, C, D and G was considered to be a new subspecies of Microbispora rosea, and the name, Microbispora rosea subsp. hibaria, was proposed. Hibarimicins A, B, C and D specifically inhibited the src tyrosine kinase activity without affecting protein kinase A or protein kinase C. They also showed in vitro anti-Gram-positive bacterial and antitumor activities. The molecular formulae of hibarimicins A, B, C, D and G were assigned to be C₈₅H₁₁₂O₃₇, C₈₅H₁₁₂O₃₇, C₈₃H₁₁₀O₃₆, C₈₅H₁₁₂O₃₈, and C₈₅H₁₁₂O₃₉ respectively.