Sorangium cellulosum KM1041이 생산하는 새로운 대사산물, Spirodienal A의 분리와 구조결정 및 생물활성

Abstract

The gram-negative myxobacteria belong to the δ-group of proteobacteria and show some outstanding and unique features. They can move by gliding or creeping on surfaces and exhibit a complex life cycle which includes the formation of fruiting bodies and culminates in the production of myxospores upon starvation. Using exoenzymes, they lyse different biological macromolecules as well as whole microorganisms such as bacteria and yeast. Over the last decades, myxobacteria have increasingly gained attention as producers of biologically active secondary metabolites which exhibit diverse molecular mechanism of action.

Especially, myxobacteria of the genus Sorangium have proved to be extremely versatile producers of biologically active secondary metabolites. This diversity is true both for the basic structures, which are generally new, and for the biological effects and their underlying mechanisms.

But, myxobacteria are not obtained by the routine method for culturing bacteria and thus require a special technique for their isolation and culture. We had succeeded in isolation of pure S. cellulosum from Korean soil. Our collection increased last year by 96 strains.

In the course of screening for new bioactive substances from several S. cellulosum isolates, strain KM1041 was found to produce bioactive compounds such as epothilones, a promising class of anticancer agent. They were isolated by silica gel column chromatography and RP­18 column chromatography, consecutively. These compounds were finally purified using semi­prep HPLC. Their structures were elucidated by detailed NMR spectroscopic analysis.

As the result of this research, a new compound, termed Spirodienal A, has been isolated. Its structure was elucidated to be novel spiroketal with a terminal dienal group.

The well known anticancer compound epothilone A was found to possess algicidal activity. It selectively inhibited the growth of the harmful cyanobacterium Microcystis aeruginosa, in a concentration dependent manner with IC_(50) of 30㎍/㎖.