Tomas Christopher A, Welker Neil E, Papoutsakis Eleftherios T
Department of Chemical Engineering, Molecular Biology, Northwestern University, Evanston, Illinois 60208, USA.
Appl Environ Microbiol. 2003 Aug;69(8):4951-65. doi: 10.1128/AEM.69.8.4951-4965.2003.
DNA array and Western analyses were used to examine the effects of groESL overexpression and host-plasmid interactions on solvent production in Clostridium acetobutylicum ATCC 824. Strain 824(pGROE1) was created to overexpress the groESL operon genes from a clostridial thiolase promoter. The growth of 824(pGROE1) was inhibited up to 85% less by a butanol challenge than that of the control strain, 824(pSOS95del). Overexpression of groESL resulted in increased final solvent titers 40% and 33% higher than those of the wild type and plasmid control strains, respectively. Active metabolism lasted two and one half times longer in 824(pGROE1) than in the wild type. Transcriptional analysis of 824(pGROE1) revealed increased expression of motility and chemotaxis genes and a decrease in the expression of the other major stress response genes. Decreased expression of the dnaKJ operon upon overexpression of groESL suggests that groESL functions as a modulator of the CIRCE regulon, which is shown here to include the hsp90 gene. Analysis of the plasmid control strain 824(pSOS95del) revealed complex host-plasmid interactions relative to the wild-type strain, resulting in prolonged biphasic growth and metabolism. Decreased expression of four DNA gyrases resulted in differential expression of many key primary metabolism genes. The ftsA and ftsZ genes were expressed at higher levels in 824(pSOS95del), revealing an altered cell division and sporulation pattern. Both transcriptional and Western analyses revealed elevated stress protein expression in the plasmid-carrying strain.
采用DNA阵列和蛋白质免疫印迹分析来检测groESL过表达以及宿主 - 质粒相互作用对丙酮丁醇梭菌ATCC 824溶剂生产的影响。构建菌株824(pGROE1)以从梭菌硫解酶启动子过表达groESL操纵子基因。与对照菌株824(pSOS95del)相比,824(pGROE1)在丁醇挑战下生长抑制降低了85%。groESL过表达导致最终溶剂滴度分别比野生型和质粒对照菌株高40%和33%。824(pGROE1)的活跃代谢持续时间比野生型长2.5倍。对824(pGROE1)的转录分析显示,运动性和趋化性基因表达增加,而其他主要应激反应基因表达减少。groESL过表达时dnaKJ操纵子表达降低,表明groESL作为CIRCE调节子的调节剂发挥作用,此处显示该调节子包括hsp90基因。对质粒对照菌株824(pSOS95del)的分析揭示了相对于野生型菌株复杂的宿主 - 质粒相互作用,导致双相生长和代谢延长。四种DNA促旋酶表达降低导致许多关键初级代谢基因的差异表达。ftsA和ftsZ基因在824(pSOS95del)中表达水平较高,揭示了细胞分裂和孢子形成模式的改变。转录分析和蛋白质免疫印迹分析均显示携带质粒的菌株中应激蛋白表达升高。