We report improved NADPH flux and xylitol biosynthesis in engineered E. coli. Xylitol is produced from xylose via an NADPH dependent reductase. We utilize two-stage dynamic metabolic control to compare two approaches to optimize xylitol biosynthesis, a stoichiometric approach, wherein competitive fluxes are decreased, and a regulatory approach wherein the levels of key regulatory metabolites are reduced. The stoichiometric and regulatory approaches lead to a 16 fold and 100 fold improvement in xylitol production, respectively. Strains with reduced levels of enoyl-ACP reductase and glucose-6-phosphate dehydrogenase, led to altered metabolite pools resulting in the activation of the membrane bound transhydrogenase and a new NADPH generation pathway, namely pyruvate ferredoxin oxidoreductase coupled with NADPH dependent ferredoxin reductase, leading to increased NADPH fluxes, despite a reduction in NADPH pools. These strains produced titers of 200 g/L of xylitol from xylose at 86% of theoretical yield in instrumented bioreactors. We expect dynamic control over enoyl-ACP reductase and glucose-6-phosphate dehydrogenase to broadly enable improved NADPH dependent bioconversions.HighlightsDecreases in NADPH pools lead to increased NADPH fluxesPyruvate ferredoxin oxidoreductase coupled with NADPH-ferredoxin reductase improves NADPH production in vivo.Dynamic reduction in acyl-ACP/CoA pools alleviate inhibition of membrane bound transhydrogenase and improve NADPH fluxXylitol titers > 200g/L in fed batch fermentations with xylose as a sole feedstock.
Background Limited data are available regarding the current microbiological characteristics of bloodstream infections (BSIs) in intensive care units (ICUs) in China. This retrospective study aimed to determine the epidemiology of early- and late-onset BSIs in our ICU. Methods We retrospectively collected data about ICU patients with BSI from 2013 to 2017. The patients were divided into the early- and late-onset BSI groups according to if BSI occurred within or beyond 48 hours after ICU admission. Univariate and multivariate logistic regression analyses were used to assess the risk factors for infection with multidrug resistant organisms (MDROs). Results Of 5474 ICU admissions, 486 (8.9%) patients with BSIs and with 500 microorganisms were included in this study, 246 (50.6%) of whom had early-onset BSIs. Two hundred and seventy patients were infected with MDROs. The proportion of MDRO infections was significantly higher among patients with late-onset BSIs than among those with early-onset BSIs (57.9% vs. 41.5%, P = .017). The ICU mortality rate was significantly higher in the late-onset BSI group (44.6% vs. 33.8%, P = .014) and early and appropriate antimicrobial treatment significantly improved the survival rate among patients with BSI (P < .001). Conclusions MDROs affected more than half of patients with BSI in the ICU. Early appropriate empirical antimicrobial therapy could improve clinical outcome of patients with BSIs.
This paper considers a multichannel deconvolution model with Gaussian white noises. The goal is to estimate the d -th derivatives of an unknown function in the model. For super-smooth case, we construct an adaptive linear wavelet estimator by wavelet projection method. For regular-smooth case, we provide an adaptive nonlinear wavelet estimator by hard-thresholded method. In order to measure the global performances of our estimators, we show upper bounds on convergence rates using the L p -risk ( 1 ≤ p < ∞ ).
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