scholarly journals Discovery of a multi-functional biocatalyst for asymmetric conjugate reduction-reductive amination

Author(s):  
Nicholas Turner ◽  
Thomas Thorpe ◽  
James Marshall ◽  
Vanessa Harawa ◽  
Rebecca Ruscoe ◽  
...  

Abstract A major challenge in chemical synthesis is to develop catalytic systems that convert simple molecules to complex high-value products. Often these valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Of great interest are enantioenriched amine diastereomers, which are prevalent in pharmaceuticals and agrochemicals,1 yet their preparation often relies on low-efficiency multi-step synthesis.2 Herein, we report the discovery and characterisation of a multi-functional biocatalyst, which operates using a previously unreported conjugate reduction-reductive amination mechanism. This enzyme (pIR-120), identified within a metagenomic imine reductase (IRED) collection3 and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates an amine-activated conjugate alkene reduction followed by reductive amination. This enzyme enables the coupling of a broad selection of α,β-unsaturated carbonyls with amines for the efficient preparation of enantioenriched amine diastereomers. Moreover, employing a racemic substrate partner or conjugated dienyl-ketone provides a means of controlling additional stereocentres using the single catalyst. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by pIR-120 which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 33
Author(s):  
Paula Brown ◽  
Marisa Battistella

The use of sustained low-efficiency dialysis (SLED) as a renal replacement modality has increased in critically ill patients with both acute kidney injury (AKI) and hemodynamic instability. Unfortunately, there is a paucity of data regarding the appropriate dosing of medications for patients undergoing SLED. Dose adjustment in SLED often requires interpretation of pharmacodynamics and pharmacokinetic factors and extrapolation based on dosing recommendations from other modes of renal replacement therapy (RRT). This review summarizes published trials of antimicrobial dose adjustment in SLED and discusses pharmacokinetic considerations specific to medication dosing in SLED. Preliminary recommendation is provided on selection of appropriate dosing for medications where published literature is unavailable.


1994 ◽  
Vol 343 (1306) ◽  
pp. 405-411 ◽  

Transmissions of bovine spongiform encephalopathy (BSE) from seven unrelated cattle sources have given remarkably uniform disease characteristics in mice, differing from over twenty previous and contemporary transmissions of sheep and goat scrapie. Transmissions to mice of spongiform encephalopathy from six species (including sheep and goats) which have been experimentally or naturally infected with bse have given similar results to direct BSE transmissions from cattle. Therefore the BSE agent has retained its identity when passaged through a range of species and the ‘donor’ species has little specific influence on disease characteristics in mice, adding to evidence for an agent-specific informational molecule. On transmission of BSE or scrapie to mice the incubation periods are long compared with subsequent mouse-to-mouse passages (the ‘species barrier’). C ontributing factors include a low efficiency of infection on interspecies transmission, the apparent failure of intracerebrally injected ‘foreign’ inoculum to establish infection directly in mouse brain and the selection of variant strains of agent which replicate most readily in the new host species.


2010 ◽  
Vol 10 ◽  
pp. 29-40
Author(s):  
T.N. Melnichuk

Microorganisms associative to the specific botanical species (Brassica capitata var. alba Lizg., Licopersicum esculentum Mill., Сucumis sativus L.) were isolated followed by the study of their morphological, physiology-biochemical properties and plants’ reaction on inoculation. It was shown that the quantity of isolated associative microorganisms’ isolations had depended both on the specie of macroorganism and microorganisms of soil in which the plant was formed, and had not depended on the quantity of microorganisms in the soil. These isolations had not showed the absolute specificity to the specific plant species. Some strains had promoted increase of overgrown and root weight of Lepidium sativum L. plants on 27,3 and 54,5 % correspondingly.


2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Van Hoa PHAM ◽  
Trung Chuyen TRAN ◽  
Hong Anh LE ◽  
Thi Thu Hoa LE ◽  
Van Viet PHAM

In surface mining operations, the operating costs of truck-shovel system constitutes 50-60% ofthe total. Only a little save in the operation costs in this system will bring large profit for the mines. Dueto many investment periods, the capacity of both trucks and shovels in Cao Son surface coal mine isdifferent. This leads to the low efficiency and the difficulty in dispatching strategy for the mine. Thispaper presents the current situation and selection of advanced dispatching strategy for increasing theefficiency trucks and shovels at this surface coal mine. The results show the detailed match factor reflectsthe state of each team of loader and trucks and should be use as the indicator for dispatching decision forthe heterogeneous truck and shovel fleet at Cao Son surface coal mine.


2021 ◽  
Vol 18 ◽  
Author(s):  
Ravi Tomar ◽  
Swati Jain ◽  
Purnima yadav ◽  
Tanima Bajaj ◽  
Fatemeh Mohajer ◽  
...  

: The natural terpene limonene is widely found in nature. The (R)-limonene (the most abundant enantiomer) is present in the essential oils of lemon, orange, and other citrus fruits, while the (S)-limonene is found in peppermint and the racemate in turpentine oil. Limonene is a low-cost, low toxicity biodegradable terpene present in agricultural wastes derived from citrus peels. The products obtained from the conversion of limonene are valuable compounds widely used as additives for food, cosmetics, or pharmaceuticals. The conversion of limonene to produce different products has been the subject of intense research, mainly with the objective to improve catalytic systems. This review focused on the application of heterogeneous catalysts in the catalytic conversion of limonene.


1986 ◽  
Vol 7 (8) ◽  
pp. 419-424 ◽  
Author(s):  
Elaine Larson ◽  
George H. Talbot

AbstractGiven the wide range of available health care personnel handwashing agents, selection of an appropriate product may be difficult. This decision may be made on the basis of user preference, cost, or other factors unrelated to product effectiveness. Four criteria—efficacy, safety, cost, and acceptability—are appropriate for systematic evaluation of handwashing products. These criteria are applied to para-chloro-meta-xylenol (PCMX), a compound used with increasing frequency in health care personnel handwashing agents. Published data regarding the biochemical properties, efficacy, and safety of PCMX are summarized. We conclude that the substance appears to be safe and efficacious. However, the activity of PCMX is highly formula-dependent and many of the studies available in scientific literature have been conducted in Europe using a variety of testing conditions and formulations different from those currently available in the US. Clinical studies of marketed formulations are beginning to appear in the literature. Such studies will provide the data needed for adequate product evaluation.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yu Zhang ◽  
Yujie Zheng ◽  
Pengguo Xia ◽  
Lulu Xun ◽  
Zongsuo Liang

Abstract Panax notoginseng is a highly regarded medicinal plant that has been cultivated for more than 400 years in Southwest China. The obstacles associated with the continuous cropping of P. notoginseng are the greatest issues for the development this plant. In the present study, the micro-ecologies of soils differing in the duration of P. notoginseng planting were compared, the results of which could provide important information to aid in solving the problems associated with the continuous cropping of P. notoginseng. Soils in which P. notoginseng had grown for 1, 3 or 5 years, as well as unplanted or fallow soil, which had a P. notoginseng planting interval of 1, 3, 6 or 9 years, were collected in Yunnan Province, China. The numbers and physiological groups of microorganisms, soil enzyme activities and nutrients present in the soil were analyzed to identify the effects of continuous cropping and determine the influence of crop rotation on the soil. After P. notoginseng was planted, the ecological structure of the soil and the balance of soil nutrients changed. These changes in the soil ecosystem prevented the soil from adapting to the continuous cropping of P. notoginseng, which eventually limited the growth of P. notoginseng and increased the incidence of diseases. After rotation of P. notoginseng, some soil indicators were restored, and some indicators with irregular changes may have been caused by crop rotation and field fertilization management practices. Thus, the selection of suitable crop rotations will facilitate the use of continuous cropping for P. notoginseng.


2015 ◽  
Vol 112 (27) ◽  
pp. 8266-8271 ◽  
Author(s):  
Haoran Zhang ◽  
Brian Pereira ◽  
Zhengjun Li ◽  
Gregory Stephanopoulos

Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an Escherichia coli-E. coli coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical cis,cis-muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. By efficiently producing another compound, 4-hydroxybenzoic acid, we also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.


Author(s):  
Léa Girard ◽  
Cédric Lood ◽  
Monica Höfte ◽  
Peter Vandamme ◽  
Hassan Rokni-Zadeh ◽  
...  

The genus Pseudomonas hosts an extensive genetic diversity and is one of the largest genera among Gram-negative bacteria. Type strains of Pseudomonas are well-known to represent only a small fraction of this diversity and the number of available Pseudomonas genome sequences is increasing rapidly. Consequently, new Pseudomonas species are regularly reported and the number of species within the genus is in constant evolution. In this study, whole genome se-quencing enabled us to define 43 new Pseudomonas species and to provide an update of the Pseu-domonas evolutionary and taxonomic relationships. Phylogenies based on the rpoD gene and whole genome sequences, including 316 and 313 type strains of Pseudomonas, respectively, re-vealed sixteen groups of Pseudomonas and justified the partitioning of the P. putida group into fifteen subgroups. Pairwise average nucleotide identities were calculated between type strains and a selection of 60 genomes of non-type strains of Pseudomonas. Forty-one strains were incor-rectly assigned at the species level and among those, 19 strains were shown to represent an addi-tional 13 new Pseudomonas species that remain to be formally classified. This work pinpoints the importance of correct taxonomic assignment and phylogenetic classification in order to perform integrative studies linking genetic diversity, lifestyle and metabolic potential of Pseudomonas spp.


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