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61.
Jan M. Klenk Paulina Dubiel Mahima Sharma Gideon Grogan Bernhard Hauer 《Microbial biotechnology》2019,12(2):377-391
One of the major challenges in chemical synthesis is the selective oxyfunctionalization of non-activated C-H bonds, which can be enabled by biocatalysis using cytochrome P450 monooxygenases. In this study, we report on the characterization of the versatile CYP109Q5 from Chondromyces apiculatus DSM436, which is able to functionalize a wide range of substrates (terpenes, steroids and drugs), including the ring of β-ionone in non-allylic positions. The crystal structure of CYP109Q5 revealed flexibility within the active site pocket that permitted the accommodation of bulky substrates, and enabled a structure-guided approach to engineering the enzyme. Some variants of CYP109Q5 displayed a switch in selectivity towards the non-allylic positions of β-ionone, allowing the simultaneous production of 2- and 3-hydroxy-β-ionone, which are chemically challenging to synthesize and are important precursors for carotenoid synthesis. An efficient whole-cell system finally enabled the production of up to 0.5 g l−1 hydroxylated products of β-ionone; this system can be applied to product identification in further biotransformations. Overall, CYP109Q5 proved to be highly evolvable and active. The studies in this work demonstrate that, using rational mutagenesis, the highly versatile CYP109Q5 generalist can be progressively evolved to be an industrially valuable specialist for the synthesis of specific products. 相似文献
62.
Paulina Bourosh Olga Bologa Nicolae Gerbeleu Maria Gdaniec 《Inorganica chimica acta》2007,360(10):3250-3254
Two complexes of gold of the compositions [Au(DMG)ClPy] (1) and [AuCl2Py2][AuCl4] · 2[AuCl3Py] (2), where H2DMG was dimethylglyoxime, were synthesized as the products of interaction of H[AuCl4] · 4H2O with H2DMG in the presence of pyridine and characterized by X-ray structural analysis. It was shown that depending on the synthetic conditions, the final product represents a molecular complex 1 or an ionic complex 2, in the latter one the charged and neutral species being combined via Au?Cl or Au?Au interactions. 相似文献
63.
Aggregation of Abeta peptides is a seminal event in Alzheimer's disease. Detailed understanding of Abeta assembly would facilitate the targeting and design of fibrillogenesis inhibitors. Here comparative conformational and aggregation studies using CD spectroscopy and thioflavine T fluorescence assay are presented. As a model peptide, the 11-28 fragment of Abeta was used. This model peptide is known to contain the core region responsible for Abeta aggregation. The structural and aggregational behaviour of the peptide was compared with the properties of its variants corresponding to natural, clinically relevant mutants at positions 21-23 (A21G, E22K, E22G, E22Q and D23N). In HFIP (hexafluoro-2-propanol), a strong alpha-helix inducer, the CD spectra revealed an unexpectedly high amount of beta-sheet conformation. The aggregation process of Abeta(11-28) variants provoked by water addition to HFIP was found to be consistent with a model of an alpha-helix-containing intermediate. The aggregation propensity of all Abeta(11-28) variants was also compared and discussed. 相似文献
64.
Changes in the redox state of the intracellular ryanodine receptor/Ca2+ release channels of skeletal and cardiac muscle or brain cortex neurons affect their activity. In particular, agents that oxidize or alkylate free SH residues of the channel protein strongly enhance Ca(2+)-induced Ca2+ release, whereas reducing agents have the opposite effects. We will discuss here how modifications of highly reactive cysteine residues by endogenous redox agents or cellular redox state influence RyR channel activation by Ca2+ and ATP or inhibition by Mg2+. Possible physiological and pathological implications of these results on cellular Ca2+ signaling will be addressed as well. 相似文献
65.
Patterns of co-occurrence of species are widely used to assess the fit of ecological neutral models to empirical patterns. The mathematically equivalent patterns of co-diversity of sites, in contrast, have been considered only indirectly and analyses normally are focused on the spatial distribution of species richness, rather than on the patterns of species sharing. Here we use two analytical tools (range-diversity plots and rank plots) to assess the predictions of simple neutral models in relation to patterns of co-occurrence and co-diversity. Whereas a fully stochastic null model predicts zero average among species and among sites, neutral models generate systems with low levels of covariance among species and high levels of positive covariance among sites. These patterns vary with different combinations of dispersal and speciation rates, but are always linked to the shape, symmetry, and spread of the range-size and species-richness frequency distributions. Non-homogeneous patterns of diversity and distribution arise in neutral models because of the spatial arrangement of sites and their concomitant similarity, which is reflected also in the spread of the range-size frequency distribution. The nearly null covariance among species, in contrast, implies low variance in species richness of sites and very slim frequency distributions. In real world assemblages of Mexican volant and non-volant mammals, patterns of range-size and species-richness frequency distribution are similar to those generated by neutral models. However, when the comparison includes the covariance both for species (co-occurrence) and for sites (co-diversity), empirical patterns differ significantly from the predictions of neutral models. Because of the mathematical links between the covariance in the distribution of species and the variance of species-richness values and between the covariance in species sharing among sites and the variance of range-size values, a full understanding of patterns of diversity calls for the simultaneous analysis of co-occurrence and co-diversity. 相似文献
66.
The titanosaur sauropod Bonatitan reigi is redescribed. The material collected, originally interpreted as pertaining to two different individuals, is reorganised in five individuals, and the original type specimen is separated into three different individuals. One of the braincases is designated as a new type specimen. Some materials are described by the first time (sacral ribs, distal caudal, chevrons, metacarpals, astragalus and metatarsals), others reinterpreted as different bones (‘ulna’ and ‘radius’). The diagnosis of B. reigi is emended, removing some of the original characters (longitudinal groove located on the suture between the parietals that continues posteriorly over the supraoccipital to the foramen magnum) and adding some new (small paired pits on the frontals and posterior ridge of the metacarpal IV). The phylogenetic analysis does not support B. reigi as a member of the Saltasaurinae, but rather as a basal member of a broad clade of sauropods that in turn is recovered as the sister group of the Saltasauridae. 相似文献
67.
Krzysztof Styczeń Magdalena Sowa-Kućma Marcin Siwek Dominika Dudek Witold Reczyński Paulina Misztak Bernadeta Szewczyk Roman Topór-Mądry Włodzimierz Opoka Gabriel Nowak 《Biological trace element research》2016,174(2):287-293
Copper may be involved in the pathophysiology of depression. Clinical data on this issue are very limited and not conclusive. The purpose of the study was to determine the copper concentration in the serum of patients with major depressive disorder and to discuss its potential clinical usefulness as a biomarker of the disease. A case–control clinical study included 69 patients with current depressive episode, 45 patients in remission and 50 healthy volunteers. Cu concentration was measured by electrothermal atomic absorption spectrometry (ETAAS). The mean serum copper level in depressed patients was slightly lower (by 11 %; not statistically significant) than in the control group. Furthermore, there was no significant difference in Cu2+ concentration between depressive episode and remission, nor between remission and control group. In the remission group were observed significant correlations between copper levels and the average number of relapses over the past years or time of remission. There was no correlation between serum copper and severity of depression, as measured by HDRS and MADRS. The obtained results showed no significant differences between the copper concentration in the blood serum of patients (both with current depressive episode and in remission) and healthy volunteers, as well as the lack of correlations between the copper level in the active stage of the disease and clinical features of the population. Our study is the first conducted on such a large population of patients, so the results may be particularly important and reliable source of knowledge about the potential role of copper in depression. 相似文献
68.
Frank Jakob Yamira Quintero Alexis Musacchio Paulina Estrada-de los Santos Lázaro Hernández Rudi F. Vogel 《Environmental microbiology》2019,21(11):4151-4165
Acetic acid bacteria (AAB) are associated with plants and insects. Determinants for the targeting and occupation of these widely different environments are unknown. However, most of these natural habitats share plant-derived sucrose, which can be metabolized by some AAB via polyfructose building levansucrases (LS) known to be involved in biofilm formation. Here, we propose two LS types (T) encoded by AAB as determinants for habitat selection, which emerged from vertical (T1) and horizontal (T2) lines of evolution and differ in their genetic organization, structural features and secretion mechanism, as well as their occurrence in proteobacteria. T1-LS are secreted by plant-pathogenic α- and γ-proteobacteria, while T2-LS genes are common in diazotrophic, plant-growth-promoting α-, β- and γ-proteobacteria. This knowledge may be exploited for a better understanding of microbial ecology, plant health and biofilm formation by sucrase-secreting proteobacteria in eukaryotic hosts. 相似文献
69.
Joana Ters Silvia Busoms Laura Perez Martín Adrin Luís‐Villarroya Paulina Flis Ana lvarez‐Fernndez Roser Tolr David E. Salt Charlotte Poschenrieder 《Plant, cell & environment》2019,42(8):2384-2398
High soil carbonate limits crop performance especially in semiarid or arid climates. To understand how plants adapt to such soils, we explored natural variation in tolerance to soil carbonate in small local populations (demes) of Arabidopsis thaliana growing on soils differing in carbonate content. Reciprocal field‐based transplants on soils with elevated carbonate (+C) and without carbonate (?C) over several years revealed that demes native to (+C) soils showed higher fitness than those native to (?C) soils when both were grown together on carbonate‐rich soil. This supports the role of soil carbonate as a driving factor for local adaptation. Analyses of contrasting demes revealed key mechanisms associated with these fitness differences. Under controlled conditions, plants from the tolerant deme A1(+C) native to (+C) soil were more resistant to both elevated carbonate and iron deficiency than plants from the sensitive T6(?C) deme native to (?C) soil. Resistance of A1(+C) to elevated carbonate was associated with higher root extrusion of both protons and coumarin‐type phenolics. Tolerant A1(+C) also had better Ca‐exclusion than sensitive T6(?C). We conclude that Arabidopsis demes are locally adapted in their native habitat to soils with moderately elevated carbonate. This adaptation is associated with both enhanced iron acquisition and calcium exclusion. 相似文献
70.
Daniel?SchmitterEmail author Paulina?Wachowicz Daniel?SageEmail author Anastasia?Chasapi Ioannis?Xenarios Viesturs?Simanis Michael?Unser 《Cell division》2013,8(1):6