The Design-Build-Test-Learn cycle for metabolic engineering of Streptomycetes

2021 ◽  
Author(s):  
Christopher M. Whitford ◽  
Pablo Cruz-Morales ◽  
Jay D. Keasling ◽  
Tilmann Weber
Keyword(s):  
Metabolic Engineering ◽  
Antimicrobial Resistance ◽  
Golden Age ◽  
Complex Molecules ◽  
Specialized Metabolites ◽  
Wide Range ◽  
Design Build ◽  
New Antibiotics ◽  
The 1950S ◽  
Biobased Production

Abstract Streptomycetes are producers of a wide range of specialized metabolites of great medicinal and industrial importance, such as antibiotics, antifungals, or pesticides. Having been the drivers of the golden age of antibiotics in the 1950s and 1960s, technological advancements over the last two decades have revealed that very little of their biosynthetic potential has been exploited so far. Given the great need for new antibiotics due to the emerging antimicrobial resistance crisis, as well as the urgent need for sustainable biobased production of complex molecules, there is a great renewed interest in exploring and engineering the biosynthetic potential of streptomycetes. Here, we describe the Design-Build-Test-Learn (DBTL) cycle for metabolic engineering experiments in streptomycetes and how it can be used for the discovery and production of novel specialized metabolites.

Antibiotic stewardship in UK surgical departments: challenges and possible solutions

2021 ◽  
pp. 1-6
Author(s):  
Rory Callan ◽  
Emily Loud
Keyword(s):  
Antimicrobial Resistance ◽  
Antibiotic Stewardship ◽  
Wide Range ◽  
The Future ◽  
New Antibiotics ◽  
Surgical Conditions ◽  
The Uk ◽  
Preoperative Prophylaxis

Antibiotics are one of the most widely used classes of drugs within hospitals in the UK. They have a wide range of uses within all surgical specialties, both as preoperative prophylaxis and for treatment of acute surgical conditions. Antimicrobial resistance has increasingly been seen as a major issue, as the production of new antibiotics has decreased and overall use worldwide has increased. With the COVID-19 pandemic increasing concerns about antimicrobial resistance, there is an ever-increasing need for action. This article examines the particular challenges of antibiotic stewardship in surgical departments within the UK, and outlines possible solutions for improving adherence and reducing the risk of antimicrobial resistance in the future.

The Many Pasts of Detective Fiction

2020 ◽  
Vol 1 (2) ◽  
pp. 157-172
Author(s):  
Thomas Leitch
Keyword(s):  
Detective Fiction ◽  
Golden Age ◽  
Public History ◽  
Detective Novel ◽  
Sherlock Holmes ◽  
Detective Story ◽  
The Past ◽  
Wide Range ◽  
Detective Novels ◽  
The Many

Building on Tzvetan Todorov's observation that the detective novel ‘contains not one but two stories: the story of the crime and the story of the investigation’, this essay argues that detective novels display a remarkably wide range of attitudes toward the several pasts they represent: the pasts of the crime, the community, the criminal, the detective, and public history. It traces a series of defining shifts in these attitudes through the evolution of five distinct subgenres of detective fiction: exploits of a Great Detective like Sherlock Holmes, Golden Age whodunits that pose as intellectual puzzles to be solved, hardboiled stories that invoke a distant past that the present both breaks with and echoes, police procedurals that unfold in an indefinitely extended present, and historical mysteries that nostalgically fetishize the past. It concludes with a brief consideration of genre readers’ own ambivalent phenomenological investment in the past, present, and future each detective story projects.

scholarly journals Whole genome-based characterisation of antimicrobial resistance and genetic diversity in Campylobacter jejuni and Campylobacter coli from ruminants

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Medelin Ocejo ◽  
Beatriz Oporto ◽  
José Luis Lavín ◽  
Ana Hurtado
Keyword(s):  
Genetic Diversity ◽  
Antimicrobial Resistance ◽  
Campylobacter Jejuni ◽  
Resistance Genes ◽  
Campylobacter Coli ◽  
Whole Genome ◽  
Northern Spain ◽  
Sequence Alignments ◽  
Phenotypic Data ◽  
Wide Range

AbstractCampylobacter, a leading cause of gastroenteritis in humans, asymptomatically colonises the intestinal tract of a wide range of animals.Although antimicrobial treatment is restricted to severe cases, the increase of antimicrobial resistance (AMR) is a concern. Considering the significant contribution of ruminants as reservoirs of resistant Campylobacter, Illumina whole-genome sequencing was used to characterise the mechanisms of AMR in Campylobacter jejuni and Campylobacter coli recovered from beef cattle, dairy cattle, and sheep in northern Spain. Genome analysis showed extensive genetic diversity that clearly separated both species. Resistance genotypes were identified by screening assembled sequences with BLASTn and ABRicate, and additional sequence alignments were performed to search for frameshift mutations and gene modifications. A high correlation was observed between phenotypic resistance to a given antimicrobial and the presence of the corresponding known resistance genes. Detailed sequence analysis allowed us to detect the recently described mosaic tet(O/M/O) gene in one C. coli, describe possible new alleles of blaOXA-61-like genes, and decipher the genetic context of aminoglycoside resistance genes, as well as the plasmid/chromosomal location of the different AMR genes and their implication for resistance spread. Updated resistance gene databases and detailed analysis of the matched open reading frames are needed to avoid errors when using WGS-based analysis pipelines for AMR detection in the absence of phenotypic data.

scholarly journals Metabolic engineering in woody plants: challenges, advances, and opportunities

aBIOTECH ◽  
2021 ◽  
Author(s):  
Shu Yu ◽  
Cody S. Bekkering ◽  
Li Tian
Keyword(s):  
Renewable Energy ◽  
Metabolic Engineering ◽  
Ecosystem Services ◽  
Plant Transformation ◽  
Woody Plants ◽  
Woody Plant ◽  
High Biomass ◽  
Generation Times ◽  
Wide Range ◽  
Biochemical Diversity

AbstractWoody plant species represent an invaluable reserve of biochemical diversity to which metabolic engineering can be applied to satisfy the need for commodity and specialty chemicals, pharmaceuticals, and renewable energy. Woody plants are particularly promising for this application due to their low input needs, high biomass, and immeasurable ecosystem services. However, existing challenges have hindered their widespread adoption in metabolic engineering efforts, such as long generation times, large and highly heterozygous genomes, and difficulties in transformation and regeneration. Recent advances in omics approaches, systems biology modeling, and plant transformation and regeneration methods provide effective approaches in overcoming these outstanding challenges. Promises brought by developments in this space are steadily opening the door to widespread metabolic engineering of woody plants to meet the global need for a wide range of sustainably sourced chemicals and materials.

scholarly journals 322. Evaluation of the BioFire® Bone and Joint Infection (BJI) Panel for the Detection of Microorganisms and Antimicrobial Resistance Genes in Synovial Fluid Specimens

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S233-S234
Author(s):  
Corrin Graue ◽  
Bryan H Schmitt ◽  
Amy Waggoner ◽  
Frederic Laurent ◽  
Lelia Abad ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Synovial Fluid ◽  
Resistance Genes ◽  
Clinical Care ◽  
Joint Infection ◽  
High Morbidity ◽  
Bone And Joint Infection ◽  
Microbiological Methods ◽  
Antimicrobial Resistance Genes ◽  
Wide Range

Abstract Background Bone and Joint Infections (BJIs) present with non-specific symptoms that may include pain, swelling, and fever and are associated with high morbidity and significant risk of mortality. BJIs can be caused by a variety of bacteria and fungi, including anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians primarily rely on culture to identify the pathogen(s) responsible for infection. The BioFire® Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) is designed to detect 15 gram-positive bacteria (including seven anaerobes), 14 gram-negative bacteria (including one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in about an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel compared to various reference methods. Methods Remnant synovial fluid specimens, which were collected for routine clinical care at 13 study sites in the US and Europe, underwent testing using an IUO version of the BioFire BJI Panel. Performance of this test was determined by comparison to Standard of Care (SoC) consisting of bacterial culture performed at each study site according to their routine procedures. Results A total of 1544 synovial fluid specimens were collected and tested with the BioFire BJI Panel. The majority of specimens were from knee joints (77.9%) and arthrocentesis (79.4%) was the most common collection method. Compared to SoC culture, overall sensitivity was 90.2% and specificity was 99.8%. The BioFire BJI Panel yielded a total of 268 Detected results, whereas SoC yielded a total of 215 positive results for on-panel analytes. Conclusion The BioFire BJI Panel is a sensitive, specific, and robust test for rapid detection of a wide range of analytes in synovial fluid specimens. The number of microorganisms and resistance genes included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the timely diagnosis and appropriate management of BJIs. Disclosures Benjamin von Bredow, PhD, BioFire (Grant/Research Support) Jennifer Dien Bard, PhD, BioFire Diagnostic (Consultant, Scientific Research Study Investigator) Bart Kensinger, PhD, BioFire Diagnostics (Employee) Benedicte Pons, PhD, bioMerieux SA (Employee) Corinne Jay, PhD, bioMerieux SA (Employee)

scholarly journals Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 438
Author(s):  
Jingru Shi ◽  
Chen Chen ◽  
Dejuan Wang ◽  
Ziwen Tong ◽  
Zhiqiang Wang ◽  
...  
Keyword(s):  
Membrane Damage ◽  
Multidrug Resistant ◽  
Peptide Antibiotics ◽  
Biofilm Inhibition ◽  
Amphipathic Peptide ◽  
Host Defense Peptides ◽  
Gram Negative ◽  
Wide Range ◽  
New Antibiotics ◽  
Low Toxicity

The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA) and blaNDM, mcr-1 and tet(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying blaNDM-5, mcr-1 or tet(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens.

scholarly journals Site-specific Umpolung amidation of carboxylic acids via triplet synergistic catalysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunyun Ning ◽  
Shuaishuai Wang ◽  
Muzi Li ◽  
Jie Han ◽  
Chengjian Zhu ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Functional Group ◽  
Amide Bond ◽  
Coupling Reagents ◽  
Complex Molecules ◽  
Bond Forming ◽  
Synergistic Catalysis ◽  
Wide Range ◽  
Amidation Reaction ◽  
Forming Methods

AbstractDevelopment of catalytic amide bond-forming methods is important because they could potentially address the existing limitations of classical methods using superstoichiometric activating reagents. In this paper, we disclose an Umpolung amidation reaction of carboxylic acids with nitroarenes and nitroalkanes enabled by the triplet synergistic catalysis of FeI2, P(V)/P(III) and photoredox catalysis, which avoids the production of byproducts from stoichiometric coupling reagents. A wide range of carboxylic acids, including aliphatic, aromatic and alkenyl acids participate smoothly in such reactions, generating structurally diverse amides in good yields (86 examples, up to 97% yield). This Umpolung amidation strategy opens a method to address challenging regioselectivity issues between nucleophilic functional groups, and complements the functional group compatibility of the classical amidation protocols. The synthetic robustness of the reaction is demonstrated by late-stage modification of complex molecules and gram-scale applications.

scholarly journals Metabolic engineering, new antibiotics and biofilm viscoelasticity

2009 ◽  
Vol 3 (1) ◽  
pp. 10-14 ◽  
Author(s):  
Craig Daniels ◽  
Manuel Espinosa-Urgel ◽  
José-Luis Niqui-Arroyo ◽  
Carmen Michán ◽  
Juan L. Ramos
Keyword(s):  
Metabolic Engineering ◽  
New Antibiotics

S. YAKOVENKO AND HIS SKILLS IN THE CONTEXT OF THE INTERPETATION OF Y. BOUTSKO’S MONO-OPERA "DIARY OF A MADMAN"

2020 ◽  
Vol 1 (2) ◽  
pp. 140-145
Author(s):  
O. A. Podguzova ◽  
Keyword(s):  
Art History ◽  
Xxth Century ◽  
Avant Garde ◽  
Great Demand ◽  
Video Recordings ◽  
Wide Range ◽  
History Of ◽  
The 1950S ◽  
Vocal Art

Sergey Borisovich Yakovenko is the People's Artist of Russia, a famous musician, vocal teacher and Doctor of Art History. He entered a bright page in the history of Russian vocal art of the XXth century. Starting from the 1950s, as a vocalist, he was in great demand for chamber vocal performances, with some of them being composed by modern musicians. Yakovenko was able to operate freely with a whole stock of expressive means, inherent for avant-garde music, allowing him to take part in the most difficult performances of the latest vocal and vocal-instrumental compositions, which manifested his inclination to the theater, to the disclosure of the dramaturgy of works. S. B. Yakovenko’s stage talent declared itself in its fullness during the performance of mono- operas, among them "Diary of a Madman" by Yuriy Butsko (1968), which received a great resonance in the theatrical life of Russia. The general content of this article is the analysis of S. B. Yakovenko’s performing skill, which gave birth to a wide range of character images, generated by the protagonist’s imagination. After the analysis of audio and video recordings of the vocalist’s performances, as well as his numerous scientific works and conversations, the author discovers several important features typical for the performing interpretation by S. B. Yakovenko. These are his vocal-dramaturgical principles and vocal-theatrical direction. In Y. Boutsko’s opera "Diary of a Madman" the unique performance palette of S. B. Yakovenko allows the singer to create eight various, rapidly interchanging images, using exclusively the resources of his voice, while being on an empty stage without props and with little or no gesture or mime.

scholarly journals Oxazolidinones as Chiral Auxiliaries in the Asymmetric 1,4-Conjugate Addition Reaction Applied to the Total Synthesis of Natural Products: A Supplemental Mini-Review

2018 ◽  
Vol 15 (1) ◽  
pp. 3-20 ◽  
Author(s):  
Vahideh Zadsirjan ◽  
Majid M. Heravi
Keyword(s):  
Total Synthesis ◽  
Biological Activities ◽  
Conjugate Addition ◽  
Chiral Auxiliary ◽  
Addition Reactions ◽  
Chiral Auxiliaries ◽  
Complex Molecules ◽  
Total Syntheses ◽  
Naturally Occurring ◽  
Wide Range

Background: The most frequently used chiral auxiliaries, oxazolidinones (Evans' oxazolidinones) have been employed in 1,4-congugate addition reactions to α,β-unsaturated carbonyl compounds. Supplementary to our previous reports in this mini-review, we attempted to underscore the applications of this strategy in a step (steps) in the total synthesis of some naturally occurring compounds exhibiting diverse biological activities. Objective: In this mini-review, we try to underscore the applications of oxazolidinones (Evans’ oxazolidinones) in 1,4-congugate addition reactions to α,β-unsaturated carbonyl in the total synthesis of some naturally occurring compounds exhibiting diverse biological activities. Conclusion: In spite of well-known superiority of asymmetric catalyzed reactions, the use of auxiliarycontrolled reactions are still considered as commanding, vital and sometimes as only tools in the generation of stereogenic centers during the construction of complex molecules and total synthesis of naturally occurring compounds. The commercial availability, or readily accessibility of a wide variety of chiral amino alcohols as starting materials to synthesize a wide range of oxazolidinones is the merits of them. In addition, the ease of removal and subjection to various and diverse stereoselective reactions make oxazolidinones as the ideal and superior chiral auxiliaries. In this regard, they were successfully used in asymmetric 1,4-conjugate addition reactions with high stereoselectivities. The high degree of asymmetric induction can be attributed to the rigid chelation of N-acyloxazolidinones with metal ions, as well as the covering of one face of the system by the bulkiness of 4-substituent. In summary, in this report, the importance of the applications of chiral oxazolidinones as suitable chiral auxiliaries in the stereoselective, 1,4-conjugate addition reactions in asymmetric synthesis and in particular, the total synthesis of naturally occurring compounds and some complex molecules were underscored. Noticeably, in these total syntheses, this chiral auxiliary is controlling the stereochemistry of a newly created stereogenic center as well as preserving the configuration of other chiral centers, which already have been presented in the precursor. General methods have been established for the attachment of the chiral auxiliary as a moiety to the substrate molecule in high to excellent yields. At the end of these reactions, this auxiliary can be easily removed leaving various desired reactive motifs for the next step in multi-step synthesis.

Sign in / Sign up

Export Citation Format

Share Document