Co-cultivation ofSorangium cellulosumstrains affects cellular growth and biosynthesis of secondary metabolite epothilones

Abstract

Sorangium cellulosum, a cellulolytic myxobacterium, is capable of producing a variety of bioactive secondary metabolites. Epothilones are anti-eukaryotic secondary metabolites produced by some S. cellulosum strains. In this study, we analyzed interactions between 12 strains of S. cellulosum consisting of epothilone-producers and non-epothilone producers isolated from two distinct soil habitats. Co-cultivation on filter papers showed that different Sorangium strains inhibited one another's growth, whereas epothilone production by the producing strains changed markedly for most (73%) pairwise mixtures. Using a quantitative polymerase chain reaction, we demonstrated that the expression of epothilone biosynthetic genes in the epothilone producers typically changed significantly when these bacteria were mixed with non-producing strains. The results indicated that intraspecies interactions between different S. cellulosum strains not only inhibited the growth of partners, but also could change epothilone production.

Allopatric integrations selectively change host transcriptomes, leading to varied expression efficiencies of exotic genes in Myxococcus xanthus

“…Among the three employed M. xanthus hosts, the yield ranges were similar in the DZ2 and DK1622 mutants, but much low in the SW504 mutants. The production abilities of epothilones in M. xanthus transposition recombinants from DZ2 or DK1622 were rather similar to that in those wild type epothilone-producing S. cellulosum strains [ 24 ]. However, in contrast to the 2:1 ratio of epothilones A to B or almost single A without B in S. cellulosum strains [ 24 ], the ratios of epothilones A–B produced in these M. xanthus producers were all approximately 1:5 (Additional file 2 : Table S1).…”

“…The production abilities of epothilones in M. xanthus transposition recombinants from DZ2 or DK1622 were rather similar to that in those wild type epothilone-producing S. cellulosum strains [ 24 ]. However, in contrast to the 2:1 ratio of epothilones A to B or almost single A without B in S. cellulosum strains [ 24 ], the ratios of epothilones A–B produced in these M. xanthus producers were all approximately 1:5 (Additional file 2 : Table S1). Compared to those previously reported epothilone-producing M. xanthus recombinants (approximately 0.1 mg/L or less) [ 10 , 11 ], some of the transposition transformants gave much higher productions under unimproved fermentation conditions.…”

Recent advances in microtubule-stabilizing agents

“…Besides the above advantages of epothilones as MSAs, they are microbial secondary metabolites with simple structures, which makes the fermentation and chemical synthesis be the major routes for getting more epothilones products since the discovery and the biological activity was confirmed. In 2013, Li et al [48] investigated the impact on the strains growth and epothilones production induced by different Sorangium cellulosum strains co-cultivation, and found that in co-cultivation can increase the epothilone production significantly than the pure cultures. While, it didn't clarify that the impacted factors of epothilones biosynthetic regulatory genes.…”

A bacterial negative transcription regulator binding on an inverted repeat in the promoter for epothilone biosynthesis

“…Epothilones are potential anticancer agents by their greater water solubility and efficacy against paclitaxel-resistant tumors [13, 14]. Researchers tried many methods to improve the epothilones yield, including co-cultivation of different strains [15], mutation and high-throughput screening of high-producing strains [16], immobilization of strains [17], heterologous expressions [18–24] and manipulation of related genes [25, 26]. However, the yield is still limited.…”