A structural and functional analysis of the glycosyltransferase BshA from Staphylococcus aureus: Insights into the reaction mechanism and regulation of bacillithiol production

Bacillithiol is a glucosamine‐derived antioxidant found in several pathogenic Gram‐positive bacteria. The compound is involved in maintaining the appropriate redox state within the cell as well as detoxifying foreign agents like the antibiotic fosfomycin. Bacillithiol is produced via the action of three enzymes, including BshA, a retaining GT‐B glycosyltransferase that utilizes UDP‐N‐acetylglucosamine and l ‐malate to produce N‐acetylglucosaminyl‐malate. Recent studies suggest that retaining GT‐B glycosyltransferases like BshA utilize a substrate‐assisted mechanism that goes through an S_Ni‐like transition state. In a previous study, we relied on X‐ray crystallography as well as computational simulations to hypothesize the manner in which substrates would bind the enzyme, but several questions about substrate binding and the role of one of the amino acid residues persisted. Another study demonstrated that BshA might be subject to feedback inhibition by bacillithiol, but this phenomenon was not analyzed further to determine the exact mechanism of inhibition. Here we present X‐ray crystallographic structures and steady‐state kinetics results that help elucidate both of these issues. Our ligand‐bound crystal structures demonstrate that the active site provides an appropriate steric and geometric arrangement of ligands to facilitate the substrate‐assisted mechanism. Finally, we show that bacillithiol is competitive for UDP‐N‐acetylglucosamine with a K_i value near 120–130 μM and likely binds within the BshA active site, suggesting that bacillithiol modulates BshA activity via feedback inhibition. The work presented here furthers our understanding of bacillithiol metabolism and can aid in the development of inhibitors to counteract resistance to antibiotics such as fosfomycin.     

Gene editing of the wheat homologs of TONNEAU1‐recruiting motif encoding gene affects grain shape and weight in wheat

Grain size and weight are important components of a suite of yield‐related traits in crops. Here, we showed that the CRISPR‐Cas9 gene editing of TaGW7, a homolog of rice OsGW7 encoding a TONNEAU1‐recruiting motif (TRM) protein, affects grain shape and weight in allohexaploid wheat. By editing the TaGW7 homoeologs in the B and D genomes, we showed that mutations in either of the two or both genomes increased the grain width and weight but reduced the grain length. The effect sizes of mutations in the TaGW7 gene homoeologs coincided with the relative levels of their expression in the B and D genomes. The effects of gene editing on grain morphology and weight traits were dosage dependent with the double‐copy mutant showing larger effect than the respective single copy mutants. The TaGW7‐centered gene co‐expression network indicated that this gene is involved in the pathways regulating cell division and organ growth, also confirmed by the cellular co‐localization of TaGW7 with α‐ and β‐tubulin proteins, the building blocks of microtubule arrays. The analyses of exome capture data in tetraploid domesticated and wild emmer, and hexaploid wheat revealed the loss of diversity around TaGW7‐associated with domestication selection, suggesting that TaGW7 is likely to play an important role in the evolution of yield component traits in wheat. Our study showed how integrating CRISPR‐Cas9 system with cross‐species comparison can help to uncover the function of a gene fixed in wheat for allelic variants targeted by domestication selection and select targets for engineering new gene variants for crop improvement.     

发酵透明质酸寡糖兽疫链球菌工程菌株的构建

透明质酸(HA)广泛应用于医学、化妆品、食品等领域。HA的生物活性取决于其分子量(M_w)。透明质酸寡糖由于具有重要的生理活性与特殊生理功能,在医药领域具有重要的应用前景。兽疫链球菌因其发酵周期短、生产强度较强的特点,在商业生产HA上具有广泛的应用。为了高效发酵合成透明质酸寡糖和解决发酵过程的溶氧问题,文中通过在兽疫链球菌WSH-24中过表达透明质酸合酶HasA以及优化表达水蛭来源的透明质酸酶LHAase。重组菌株摇瓶发酵24h,透明质酸寡糖积累至0.97g/L,比野生菌提高了182.0%。在3L发酵罐中发酵24 h,透明质酸寡糖生产强度为294.2 mg/(L·h),HA积累至7.06 g/L,比野生菌的罐上水平提高了112.4%。文中所构建的发酵合成透明质酸寡糖的兽疫链球菌重组菌株具有重要的应用前景。     

Morphological variation associated with dispersal capacity in a tree‐killing bark beetle Dendroctonus ponderosae Hopkins

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A metabolome‐based core hybridisation strategy for the prediction of rice grain weight across environments

Marker‐based prediction holds great promise for improving current plant and animal breeding efficiencies. However, the predictabilities of complex traits are always severely affected by negative factors, including distant relatedness, environmental discrepancies, unknown population structures, and indeterminate numbers of predictive variables. In this study, we utilised two independent F₁ hybrid populations in the years 2012 and 2015 to predict rice thousand grain weight (TGW) using parental untargeted metabolite profiles with a partial least squares regression method. A stable predictive model for TGW was built based on hybrids from the population in 2012 (r = 0.75) but failed to properly predict TGW for hybrids from the population in 2015 (r = 0.27). After integrating hybrids from both populations into the training set, the TGW of hybrids could be predicted but was largely dependent on population structures. Then, core hybrids from each population were determined by principal component analysis and the TGW of hybrids in both environments were successfully predicted (r > 0.60). Moreover, adjusting the population structures and numbers of predictive analytes increased TGW predictability for hybrids in 2015 (r = 0.72). Our study demonstrates that the TGW of F₁ hybrids across environments can be accurately predicted based on parental untargeted metabolite profiles with a core hybridisation strategy in rice. Metabolic biomarkers identified from early developmental stage tissues, which are grown under experimental conditions, may represent a workable approach towards the robust prediction of major agronomic traits for climate‐adaptive varieties.     

Comparative population genomics identified genomic regions and candidate genes associated with fruit domestication traits in peach

Crop evolution is a long‐term process involving selection by natural evolutionary forces and anthropogenic influences; however, the genetic mechanisms underlying the domestication and improvement of fruit crops have not been well studied to date. Here, we performed a population structure analysis in peach (Prunus persica) based on the genome‐wide resequencing of 418 accessions and confirmed the presence of an obvious domestication event during evolution. We identified 132 and 106 selective sweeps associated with domestication and improvement, respectively. Analysis of their tissue‐specific expression patterns indicated that the up‐regulation of selection genes during domestication occurred mostly in fruit and seeds as opposed to other organs. However, during the improvement stage, more up‐regulated selection genes were identified in leaves and seeds than in the other organs. Genome‐wide association studies (GWAS) using 4.24 million single nucleotide polymorphisms (SNPs) revealed 171 loci associated with 26 fruit domestication traits. Among these loci, three candidate genes were highly associated with fruit weight and the sorbitol and catechin content in fruit. We demonstrated that as the allele frequency of the SNPs associated with high polyphenol composition decreased during peach evolution, alleles associated with high sugar content increased significantly. This indicates that there is genetic potential for the breeding of more nutritious fruit with enhanced bioactive polyphenols without disturbing a harmonious sugar and acid balance by crossing with wild species. This study also describes the development of the genomic resources necessary for evolutionary research in peach and provides the large‐scale characterization of key agronomic traits in this crop species.     

Post-translational modifications in MeHg-induced neurotoxicity

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.     

Introduced cats Felis catus eating a continental fauna: inventory and traits of Australian mammal species killed

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Resource pulses affect prey selection and reduce dietary diversity of dingoes in arid Australia

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基于层次分析法对白垩纪短脉螽科昆虫后足胫节端距的游泳能力检测

短脉螽科是直翅目昆虫的一个中生代灭绝类群,其最重要特征之一是后足胫节末端具有3—4根较长的距,可以分为长刺状、棒状和叶状等3种类型。在假设短脉螽科具有游泳能力条件下,利用层次分析法(Analytic Hierarchy Process,AHP)探讨短脉螽不同后足胫节端距类型对游泳能力的贡献。分析表明短脉螽科昆虫中,具有叶状端距的类型更有利于提高该类昆虫的游泳能力。短脉螽科昆虫后足端距的高分异度,表明该科昆虫在白垩纪的近水环境不同生态位中均具有较好的适应性。