Allosamidin 1, a secondary metabolite of Streptomyces, inhibits family 18 chitinases which are widely present in nature. Allosamidin has been used to study the physiological role of chitinases in a variety of organisms. With respect to its biological activity toward mammals, 1 attenuates asthmatic responses in asthma models of mouse. On the other hand, 1 dramatically promotes chitinase production and growth of its producing microorganism. 1 was released from the mycelia of allosamidin-producing Streptomyces by responding to chitin and strongly activated transcription of a gene encoding the main chitinase secreted to the culture broth through a two-component regulatory system in the presence of N,N'-diacetylchitobiose. This shows that 1 acts as a key signal molecule for chitinase production in its producing strains, which may be useful for their growth in chitin-rich environment. Effects of 1 and demethylallosamidin 2 on the activity of acidic mammalian chitinase (AMCase) and asthmatic inflammation were examined. 2 inhibited recombinant AMCase as strongly as allosamidin. In the mouse in vivo model of IL-13-induced asthma, both 1 and 2 decreased chitinase activity and eosinophils in BAL (bronchoalveolar lavage) fluid. Only 2, however, showed suppressive activity on airway hyperresponsiveness, suggessting that 2 may suppress IL-13-induced asthma more effectively than 1.
