A fungal nonribosomal peptide synthetase module that can synthesize thiopyrazines

A nonribosomal peptide synthetase-like enzyme (NRPS325) from Aspergillus terreus was reconstituted in vitro and was shown to synthesize thiopyrazines using an unprecedented mechanism. Substrate promiscuity of NRPS325 toward different amino acids and free thiols was explored to produce >60 different thiopyrazine compounds.     

Compound I in heme thiolate enzymes: a comparative QM/MM study

This study directly compares the active species of heme enzymes, so-called Compound I (Cpd I), across the heme-thiolate enzyme family. Thus, sixty-four different Cpd I structures are calculated by hybrid quantum mechanical/molecular mechanical (QM/MM) methods using four different cysteine-ligated heme enzymes (P450(cam), the mutant P450(cam)-L358P, CPO and NOS) with varying QM region sizes in two multiplicities each. The overall result is that these Cpd I species are similar to each other with regard to many characteristic features. Hence, using the more stable CPO Cpd I as a model for P450 Cpd I in experiments should be a reasonable approach. However, systematic differences were also observed, and it is shown that NOS stands out in most comparisons. By analyzing the electrical field generated by the enzyme on the QM region, one can see that (a) the protein exerts a large influence and modifies all the Cpd I species compared with the gas-phase situation and (b) in NOS this field is approximately planar to the heme plane, whereas it is approximately perpendicular in the other enzymes, explaining the deviating results on NOS. The calculations on the P450(cam) mutant L358P show that the effects of removing the hydrogen bond between the heme sulfur and L358 are small at the Cpd I stage. Finally, Mossbauer parameters are calculated for the different Cpd I species, enabling future comparisons with experiments. These results are discussed in the broader context of recent findings of Cpd I species that exhibit large variations in the electronic structure due to the presence of the substrate.     

Solvent-free and catalyst-free method for the synthesis of 2,4,5-triarylimidazoles under microwave irradiation

A facile procedure for the synthesis of 2,4,5-triarylimidazoles is being reported starting from benzil, aromatic aldehyde and ammonium acetate. The reactions were carried out with catalyst-free, solvent-free and under microwave irradiation conditions in high yield (80–99%) with short time (3–5 min) and environmental benign, as well as convenient operation. The structures of the compounds have been confirmed on the basis of their IR, ¹H NMR, and/or ¹³C NMR, MS, and elemental analyzer.     

Nanosheet‐Enhanced Asymmetric Induction of Chiral α‐Amino Acids in Catalytic Aldol Reaction

An efficient ligand design strategy towards boosting asymmetric induction was proposed, which simply employed inorganic nanosheets to modify α‐amino acids and has been demonstrated to be effective in vanadium‐catalyzed epoxidation of allylic alcohols. Here, the strategy was first extended to zinc‐catalyzed asymmetric aldol reaction, a versatile bottom‐up route to make complex functional compounds. Zinc, the second‐most abundant transition metal in humans, is an environment‐friendly catalytic center. The strategy was then further proved valid for organocatalyzed metal‐free asymmetric catalysis, that is, α‐amino acid catalyzed asymmetric aldol reaction. Visible improvement of enantioselectivity was experimentally achieved irrespective of whether the nanosheet‐attached α‐amino acids were applied as chiral ligands together with catalytic Zn^II centers or as chiral catalysts alone. The layered double hydroxide nanosheet was clearly found by theoretical calculations to boost ee through both steric and H‐bonding effects; this resembles the role of a huge and rigid substituent.     

A Novel Total Synthesis of (±)Shikonin

Shikonin 1 was a key component isolated from the traditional Chinese herbal medicine, Zicao(Lithospermum erythrorhizon Sieb.et Zucc), which possesses multiple biological activities1. There have been many synthetic routes to shikonin, however, all these ro…     

Capillary electrophoresis with direct chemiluminescence detection for the analysis of catecholamines in human urine

A rapid and sensitive method for the analysis of three catecholamines by capillary electrophoresis(CE)with directchemiluminescence(CL)detection is described.The detection limits(S/N=3)were 1.3*10-8g/mL for isoprenaline,1.0*10-8g/mL for epinephrine and 2.8*10-8g/mL for dopamine.The proposed method was successfully applied to theanalysis of catecholamines in urine samples of cigarette smokers and nonsmokers.The results showed that there is a close relationbetween the release of dopamine in human body fluids and cigarette smoking/nonsmoking.     

High-throughput lipidomics analysis to discover lipid biomarkers and profiles as potential targets for evaluating efficacy of Kai-Xin-San against APP/PS1 transgenic mice based on UPLC–Q/TOF–MS

Lipid metabolism has a significant function in the central nervous system and Alzheimer's disease (AD) is an age-related senile disease characterized by central nerve degeneration. The pathological development of AD is closely related to lipid metabolism disorders. To reveal the influence of Kai-Xin-San (KXS) on lipid metabolism in APP/PSI transgenic mice and potential therapeutic targets for treating AD, brain tissue samples were collected and analyzed by high-throughput lipidomics based on UPLC–Q/TOF-MS. The collected raw data were processed by multivariate data analysis to discover the potential biomarkers and lipid metabolic profiles. Compared with the control wild-type mouse group, nine potential lipid biomarkers were found in the AD model group, of which seven were up-regulated and two were down-regulated. Orally administrated KXS can reverse the changes in these potential biomarkers. Compared with the model group, a total of six differential metabolites showed a recovery trend and may be potential targets for KXS to treat AD. This study showed that high-throughput lipidomics can be used to discover the perturbed pathways and lipid biomarkers as potential targets to reveal the therapeutic effects of KXS.     

Ugi/SmI_2还原反应合成N-取代β,γ-不饱和酰胺的研究

将α,β-不饱和醛、苯胺、乙酸和异腈的Ugi四组分反应产物在四氢呋喃中用SmI2/HMPA处理,可以得到碳链延长一位的β,γ-不饱和酰胺,方法简便,产率中等到良好.该反应涉及一个自由基脱氨基过程.     

Inferring Minimal Feasible Metabolic Networks of <Emphasis Type=Italic>Escherichia coli</Emphasis>

Since the organism contains many redundant reactions, the minimal feasible metabolic network that contains the basic growth function is not the collection of reactions that associate the essential genes. To identify minimal metabolic reaction set is a challenging work in theoretical approach. A new method is presented here to identify the smallest required reaction set of growth-sustaining metabolic networks. The content and number of the minimal reactions for growth are variable in different random processes. Though the different carbon sources also vary the content of the reactions in the minimal metabolic networks, most essential reactions locate in the same metabolic subsystems, such as cofactor and prosthetic group biosynthesis, cell envelope biosynthesis, and membrane lipid metabolism.