高效合成葡萄糖二酸酿酒酵母工程菌的构建

葡萄糖二酸是天然存在的一种重要二元酸,其在医疗保健和化工工业等领域具有很高的实际应用价值,因此被称为“最具价值的生物炼制产品之一”。以酿酒酵母(Saccharomyces cerevisiae)为底盘微生物,文中考察了过量表达肌醇转运蛋白Itr1、融合表达肌醇加氧酶和葡萄糖醛酸脱氢酶以及弱化表达葡萄糖6-磷酸脱氢酶基因ZWF1三种策略对葡萄糖二酸产量的影响。研究结果显示,过量表达肌醇转运蛋白Itr1使葡萄糖二酸产量在摇瓶发酵条件下较出发菌株Bga-3提高了26%;MIOX4-Udh融合蛋白的表达使葡萄糖二酸的产量较Bga-3菌株提高了40%;在此基础上,弱化表达葡萄糖6-磷酸脱氢酶基因ZWF1后,葡萄糖二酸的产量达5.5 g/L,较相同发酵条件下Bga-3菌株提高了60%。在5 L发酵罐中,该菌株葡萄糖二酸的最高产量达10.85 g/L,较Bga-3菌株提高了80%。由此可见,上述代谢改造策略的应用在很大程度上提高了葡萄糖二酸的途径效率和产量,为通过代谢工程方法在酿酒酵母中合成其他化合物的研究提供了参考。     

Metabolic approaches to understanding climate change impacts on seasonal host‐macroparasite dynamics

Climate change is expected to alter the dynamics of infectious diseases around the globe. Predictive models remain elusive due to the complexity of host–parasite systems and insufficient data describing how environmental conditions affect various system components. Here, we link host–macroparasite models with the Metabolic Theory of Ecology, providing a mechanistic framework that allows integrating multiple nonlinear environmental effects to estimate parasite fitness under novel conditions. The models allow determining the fundamental thermal niche of a parasite, and thus, whether climate change leads to range contraction or may permit a range expansion. Applying the models to seasonal environments, and using an arctic nematode with an endotherm host for illustration, we show that climate warming can split a continuous spring‐to‐fall transmission season into two separate transmission seasons with altered timings. Although the models are strategic and most suitable to evaluate broad‐scale patterns of climate change impacts, close correspondence between model predictions and empirical data indicates model applicability also at the species level. As the application of Metabolic Theory considerably aids the a priori estimation of model parameters, even in data‐sparse systems, we suggest that the presented approach could provide a framework for understanding and predicting climatic impacts for many host–parasite systems worldwide.     

Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage

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YAP1 and PRDM14 converge to promote cell survival and tumorigenesis

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Engineering Halomonas TD01 for the low-cost production of polyhydroxyalkanoates

The halophile Halomonas TD01 and its derivatives have been successfully developed as a low-cost platform for the unsterile and continuous production of chemicals. Therefore, to increase the genetic engineering stability of this platform, the DNA restriction/methylation system of Halomonas TD01 was partially inhibited. In addition, a stable and conjugative plasmid pSEVA341 with a high-copy number was constructed to contain a LacI^q-P_trc system for the inducible expression of multiple pathway genes. The Halomonas TD01 platform, was further engineered with its 2-methylcitrate synthase and three PHA depolymerases deleted within the chromosome, resulting in the production of the Halomonas TD08 strain. The overexpression of the threonine synthesis pathway and threonine dehydrogenase made the recombinant Halomonas TD08 able to produce poly(3-hydroxybutyrate-co-3-hydroxyvalerate) or PHBV consisting of 4–6 mol% 3-hydroxyvalerate or 3HV, from various carbohydrates as the sole carbon source. The overexpression of the cell division inhibitor MinCD during the cell growth stationary phase in Halomonas TD08 elongated its shape to become at least 1.4-fold longer than its original size, resulting in enhanced PHB accumulation from 69 wt% to 82 wt% in the elongated cells, further promoting gravity-induced cell precipitations that simplify the downstream processing of the biomass. The resulted Halomonas strains contributed to further reducing the PHA production cost.     

Effect of natural exogenous antioxidants on aging and on neurodegenerative diseases

Abstract

Aging and neurodegenerative diseases share oxidative stress cell damage and depletion of endogenous antioxidants as mechanisms of injury, phenomena that are occurring at different rates in each process. Nevertheless, as the central nervous system (CNS) consists largely of lipids and has a poor catalase activity, a low amount of superoxide dismutase and is rich in iron, its cellular components are damaged easily by overproduction of free radicals in any of these physiological or pathological conditions. Thus, antioxidants are needed to prevent the formation and to oppose the free radicals damage to DNA, lipids, proteins, and other biomolecules. Due to endogenous antioxidant defenses are inadequate to prevent damage completely, different efforts have been undertaken in order to increase the use of natural antioxidants and to develop antioxidants that might ameliorate neural injury by oxidative stress. In this context, natural antioxidants like flavonoids (quercetin, curcumin, luteolin and catechins), magnolol and honokiol are showing to be the efficient inhibitors of the oxidative process and seem to be a better therapeutic option than the traditional ones (vitamins C and E, and β-carotene) in various models of aging and injury in vitro and in vivo conditions. Thus, the goal of the present review is to discuss the molecular basis, mechanisms of action, functions, and targets of flavonoids, magnolol, honokiol and traditional antioxidants with the aim of obtaining better results when they are prescribed on aging and neurodegenerative diseases.     

Effect of Adding Branched-chain Amino Acids to a Nicotinic Acid-free,Low-protein Diet on the Conversion Ratio of Tryptophan to Nicotinamide in Rats

The effects of adding branched-chain amino acids to a nicotinic acid-free, low-protein diet on the conversion of tryptophan to nicotinamide were investigated in rats. The conversion ratio [urinary excretion of nicotinamide and its metabolites (μmol/day) × 100/tryptophan intake during urine collection (μmol/day)] was significantly lower in the groups fed with the 3% Leu-, Val-, or Ile-added diet than in the group fed with the control diet. Namely, the inhibition of this conversion was observed not only by the addition of Leu, but also by the addition of Val or Ile. The addition of Ile and/or Val to the Leu-added diet did not antagonize the Leu effect.     

A Comparative Analysis of the Synergistic Interaction Between N'-Phenylsulfanilamides and Benzylpyrimidines Using Qsar Techniques

Abstract

Growth inhibition of E. coli cell culture has been determined for a series of 4-substituted-N'-phenylsulfonamides tested in the presence and absence of synergistic concentrations of trimethoprim. Quantitative structure-activity relationships, established by regression analysis, exhibit an identical dependence of bacterial growth inhibition on sulfonamide pK_a irrespective of the presence or absence of trimethoprim. Examination of a small series of benzylpyrimidines in the presence or absence of 4-dimethylamino-N¹-phenylsulfanilamide gave similar results. Since the presence of a synergistic agent affords no change in structure-activity relationships, it is concluded that no direct interaction between sulfonamides and benzylpyrimidines occurs and that the synergism observed is solely the result of the kinetic consequences of sequential blockade of the folate biosynthetic pathway.