RESUMO
This review details the isolation, biosynthesis, biological activity and synthesis of spiroacetals from the myxobacterium Sorangium cellulosum. The strategies utilised to access the challenging structures and stereochemistry of these natural products are highlighted.
Assuntos
Acetais/metabolismo , Produtos Biológicos/metabolismo , Compostos de Espiro/metabolismo , Acetais/química , Produtos Biológicos/química , Conformação Molecular , Sorangium/química , Sorangium/metabolismo , Compostos de Espiro/química , EstereoisomerismoRESUMO
Starvation induces cell aggregation in the soil bacterium Myxococcus xanthus, followed by formation of fruiting bodies packed with myxospores. Sporulation in the absence of fruiting bodies can be artificially induced by high concentrations of glycerol through unclear mechanisms. Here, we show that a compound (ambruticin VS-3) produced by a different myxobacterium, Sorangium cellulosum, affects the development of M. xanthus in a similar manner. Both glycerol (at millimolar levels) and ambruticin VS-3 (at nanomolar concentrations) inhibit M. xanthus fruiting body formation under starvation, and induce sporulation in the presence of nutrients. The response is mediated in M. xanthus by three hybrid histidine kinases (AskA, AskB, AskC) that form complexes interacting with two major developmental regulators (MrpC, FruA). In addition, AskB binds directly to the mrpC promoter in vitro. Thus, our work indicates that the AskABC-dependent regulatory pathway mediates the responses to ambruticin VS-3 and glycerol. We hypothesize that production of ambruticin VS-3 may allow S. sorangium to outcompete M. xanthus under both starvation and growth conditions in soil.
Assuntos
Glicerol/farmacologia , Myxococcales/metabolismo , Myxococcus xanthus/efeitos dos fármacos , Myxococcus xanthus/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/genética , Histidina Quinase/genética , Histidina Quinase/metabolismo , Espectrometria de Massas , Myxococcus xanthus/metabolismo , Myxococcus xanthus/fisiologia , Regiões Promotoras Genéticas , Ligação Proteica , Transdução de Sinais/fisiologia , Sorangium/química , Sorangium/metabolismo , Esporos Bacterianos , Estresse Fisiológico , Ressonância de Plasmônio de Superfície , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Epothilone is a macrolide secondary metabolite which has the same anticancer effect as paclitaxel. Based on a series of single-factor experiments, four factors, temperature, initial pH, rotation speed, and inoculum quantity, which have the greatest influence on yield, were determined. Four factors were designed and orthogonal experiments were carried out to optimize the fermentation conditions. Finally, the best experimental conditions were obtained as follows: 250 ml flapper triangular flask was used. The yield of epothilone B was 39.76 mg/L at 30â, initial pH = 7.4, rotating speed 200 r/min, inoculation amount 10%, liquid loading amount 50 ml/250 ml, fermentation time 6 days and seed age 60 hr.