Metabolic regulation of an fnr gene knockout Escherichia coli under oxygen limitation.

In addition to our previous study on the effect of fnr gene knockout on the metabolism in Escherichia coli under aerobic conditions (Kumar and Shimizu, Microb Cell Fact 2011), here we further investigated the effect of fnr gene knockout on the metabolism under micro-aerobic condition based on gene expressions, enzyme activities and intracellular metabolic fluxes. The objective of the present research is to clarify the metabolic regulation mechanism on how the culture environment, such as oxygen level, affects the cell metabolism in relation to gene expressions, enzyme activities and fluxes via global regulators such as Fnr and ArcA/B systems. Under micro-aerobic condition, the flux through Pfl and Frd were reduced for the mutant, which are due to fnr gene knockout.

Effect of cra gene knockout together with edd and iclR genes knockout on the metabolism in Escherichia coli.

To elucidate the physiological adaptation of Escherichia coli due to cra gene knockout, a total of 3,911 gene expressions were investigated by DNA microarray for continuous culture. About 50 genes were differentially regulated for the cra mutant. TCA cycle and glyoxylate shunt were down-regulated, while pentose phosphate (PP) pathway and Entner Doudoroff (ED) pathway were up-regulated in the cra mutant.

An oxazole-based small-molecule Stat3 inhibitor modulates Stat3 stability and processing and induces antitumor cell effects.

Stat3 is hyperactivated in many human tumors and represents a valid target for anticancer drug design. We present a novel small-molecule Stat3 inhibitor, S3I-M2001, and describe the dynamics of intracellular processing of activated Stat3 within the context of the biochemical and biological effects of the Stat3 inhibitor. S3I-M2001 is an oxazole-based peptidomimetic of the Stat3 Src homology (SH) 2 domain-binding phosphotyrosine peptide that selectively disrupts active Stat3:Stat3 dimers.

Effect of a pyruvate kinase (pykF-gene) knockout mutation on the control of gene expression and metabolic fluxes in Escherichia coli.

The metabolic regulation of Escherichia coli lacking a functional pykF gene was investigated based on gene expressions, enzyme activities, intracellular metabolite concentrations and the metabolic flux distribution obtained based on (13)C-labeling experiments. RT-PCR revealed that the glycolytic genes such as glk, pgi, pfkA and tpiA were down regulated, that ppc, pckA, maeB and mdh genes were strongly up-regulated, and that the oxidative pentose phosphate pathway genes such as zwf and gnd were significantly up-regulated in the pykF mutant. The catabolite repressor/activator gene fruR was up-regulated in the pykF mutant, but the adenylate cyclase gene cyaA was down-regulated indicating a decreased rate of glucose uptake.