Isolation of tubulysins from myxobacteria.

Abstract

Myxobacteria are prokaryotes found commonly in soil that produces fruiting bodies and a diverse array of secondary metabolites. Tubulysins are highly potent anticancer compounds that are produced by most myxobacteria. Tubulysins disrupt microtubule networks of cancer cells leading to their inability to replicate and eventually cell death. A variety of myxobacteria strains were isolated from all three suborders of myxobacteria in the soils in Singapore. Metabolites from four isolated strains had cytotoxic effect on HeLa cells after incubation for 72 hours. Their crude extracts caused the diminishing of fluorescence of tubulins after 5 hours incubation and had greater effect after 24 hours incubation. HPLC showed high intensity peaks from 20 minutes to around 80 minutes. Mass spectrometry results revealed the presence of peaks which could be derivatives of pre-tubulysin A (pre-tub A) and tubulysin D (tub D). All four strains happened to belong to the suborder of Cystobacterineae, which is the reported tubulysin-producing suborder. This provided a basis for future research to be done with these four strains for the isolation of potential tubulysins to be used in cancer therapy.