Discovery of an Antibiotic-Related Small Protein of Biocontrol Strain Pseudomonas sp. Os17 by a Genome-Mining Strategy

Many root-colonizing Pseudomonas spp. exhibiting biocontrol activities produce a wide range of secondary metabolites that exert antibiotic effects against other microbes, nematodes, and insects in the rhizosphere. The expression of these secondary metabolites depends on the Gac/Rsm signal transduction pathway. Based on the findings of a previous genomic study on newly isolated biocontrol pseudomonad strains, we herein investigated the novel gene cluster OS3, which consists of four genes (Os1348–Os1351) that are located upstream of putative efflux transporter genes (Os1352–Os1355). Os1348 was predicted to encode an 85-aa small precursor protein, the expression of which was under the control of GacA, and an X-ray structural analysis suggested that the Os1348 protein formed a dimer. The mutational loss of the Os1348 gene decreased the antibiotic activity of Pseudomonas sp. Os17 without changing its growth rate. The Os1349–1351 genes were predicted to be involved in post-translational modifications. Intracellular levels of the Os1348 protein in the deficient mutant of each gene differed from that in wild-type cells. These results suggest that Os1348 is involved in antibiotic activity and that the structure or expression of this protein is under the control of downstream gene products.

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SeMPI 2.0—A Web Server for PKS and NRPS Predictions Combined with Metabolite Screening in Natural Product Databases

Metabolites ◽

10.3390/metabo11010013 ◽

2020 ◽

Vol 11 (1) ◽

pp. 13

Author(s):

Paul F. Zierep ◽

Adriana T. Ceci ◽

Ilia Dobrusin ◽

Sinclair C. Rockwell-Kollmann ◽

Stefan Günther

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Building Block ◽

Web Server ◽

Gene Clusters ◽

Type I ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

A Genome ◽

Wide Range

Microorganisms produce secondary metabolites with a remarkable range of bioactive properties. The constantly increasing amount of published genomic data provides the opportunity for efficient identification of biosynthetic gene clusters by genome mining. On the other hand, for many natural products with resolved structures, the encoding biosynthetic gene clusters have not been identified yet. Of those secondary metabolites, the scaffolds of nonribosomal peptides and polyketides (type I modular) can be predicted due to their building block-like assembly. SeMPI v2 provides a comprehensive prediction pipeline, which includes the screening of the scaffold in publicly available natural compound databases. The screening algorithm was designed to detect homologous structures even for partial, incomplete clusters. The pipeline allows linking of gene clusters to known natural products and therefore also provides a metric to estimate the novelty of the cluster if a matching scaffold cannot be found. Whereas currently available tools attempt to provide comprehensive information about a wide range of gene clusters, SeMPI v2 aims to focus on precise predictions. Therefore, the cluster detection algorithm, including building block generation and domain substrate prediction, was thoroughly refined and benchmarked, to provide high-quality scaffold predictions. In a benchmark based on 559 gene clusters, SeMPI v2 achieved comparable or better results than antiSMASH v5. Additionally, the SeMPI v2 web server provides features that can help to further investigate a submitted gene cluster, such as the incorporation of a genome browser, and the possibility to modify a predicted scaffold in a workbench before the database screening.

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Transporter Gene-mediated Typing for Detection and Genome Mining of Lipopeptide-producing Pseudomonas

Applied and Environmental Microbiology ◽

10.1128/aem.01869-21 ◽

2021 ◽

Author(s):

Léa Girard ◽

Niels Geudens ◽

Brent Pauwels ◽

Monica Höfte ◽

José C. Martins ◽

...

Keyword(s):

Genome Mining ◽

Chemical Characterization ◽

Gene Clusters ◽

Amplicon Sequencing ◽

Chemical Diversity ◽

Ecological Niches ◽

Transporter Gene ◽

A Genome ◽

Wide Range ◽

Suitable Target

Pseudomonas lipopeptides (LPs) are involved in diverse ecological functions and have biotechnological potential associated with their antimicrobial and/or anti-proliferative activities. They are synthesized by multi-modular non-ribosomal peptide synthetases which, together with transport and regulatory proteins, are encoded by large biosynthetic gene clusters (BGCs). These secondary metabolites are classified in distinct families based on sequence and length of the oligopeptide, and size of the macrocycle, if present. Phylogeny of PleB, the MacB-like transporter that is part of a dedicated ATP-dependent tripartite efflux system driving export of Pseudomonas LPs, revealed a strong correlation with LP chemical diversity. As each LP BGC carries its cognate pleB , PleB is suitable as a diagnostic sequence for genome mining, allowing assignment of the putative metabolite to a particular LP family. In addition, pleB proved a suitable target gene for an alternative PCR method to detect LP-producing Pseudomonas , not relying on amplification of catalytic domains of the biosynthetic enzymes. Combined with amplicon sequencing, this approach enabled typing of Pseudomonas strains as potential producers of a LP belonging to one of ten different families, underscoring its value for strain prioritization. This was validated by chemical characterization of known LPs from three different families secreted by novel producers isolated from the rice or maize rhizosphere, namely the type strains of Pseudomonas fulva (putisolvin), Pseudomonas zeae (tensin) and Pseudomonas xantholysinigenes (xantholysin). In addition, a new member of the Bananamide family, prosekin, was discovered in the type strain of Pseudomonas prosekii , an Antarctic isolate. Importance Pseudomonas are ubiquitous bacteria able to thrive in a wide range of ecological niches and lipopeptides often support their lifestyle but also their interaction with other micro- and macro-organisms. Therefore, the production of lipopeptides is widespread among Pseudomonas strains. Consequently, Pseudomonas lipopeptide research affects not only chemists and microbiologists but touches a much broader audience, including biochemists, ecologists and plant biologists. In this study we present a reliable transporter gene-guided approach for the detection and/or typing of Pseudomonas lipopeptide producers. Indeed, it allows to readily assess the lipopeptide diversity among sets of Pseudomonas isolates and differentiate strains likely to produce known lipopeptides from producers of potentially novel lipopeptides. This work provides a valuable tool that can also be integrated in a genome mining strategy and adapted for the typing of other specialized metabolites.

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(Z)-5-(3′,4′-Bis(benzyloxy)benzylidene)furan-2(5H)-one

Molbank ◽

10.3390/m1193 ◽

2021 ◽

Vol 2021 (1) ◽

pp. M1193

Author(s):

Angelica Artasensi ◽

Giovanna Baron ◽

Giulio Vistoli ◽

Giancarlo Aldini ◽

Laura Fumagalli

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Good Yield ◽

Biological Activities ◽

The Novel ◽

One Pot ◽

Natural Form ◽

Bioactive Natural Products ◽

Beneficial Effects ◽

Wide Range

Over the years secondary metabolites have been considered as lead molecules both in their natural form and as templates for medicinal chemistry. Some secondary metabolites such as polyphenols and flavan-3-ols exert beneficial effects after a modification by the microbiota. Synthetic precursors of some of these modified compounds, in turn, carried a γ-alkylidenebutenolide moiety which characterizes a large class of bioactive natural products endowed with a wide range of biological activities. For these reasons stereoselective preparation of γ-alkylidenebutenolide continues to be an important issue for organic chemists. Our objective is to synthetize the novel compound (Z)-5-(3′,4′-bis(benzyloxy)benzylidene)furan-2(5H)-one in a stereocontrolled-one-pot reaction. The product was obtained in good yield. Furthermore, the theoretical investigation of the transition states suggests a new procedure to achieve Z-isomer of β-unsubstituted γ-alkylidenebutenolide.

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A mecC allotype, mecC3, in the CoNS Staphylococcus caeli, encoded within a variant SCCmecC

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dky502 ◽

2018 ◽

Vol 74 (3) ◽

pp. 547-552 ◽

Cited By ~ 4

Author(s):

A C MacFadyen ◽

E M Harrison ◽

I Drigo ◽

J Parkhill ◽

M A Holmes ◽

...

Keyword(s):

Animal Species ◽

Methicillin Resistance ◽

Comparative Genomic ◽

The Novel ◽

Sccmec Element ◽

Genomic Context ◽

Staphylococcal Species ◽

Genomic Study ◽

Wide Range ◽

Comparative Genomic Study

AbstractBackgroundMethicillin resistance in staphylococci is conferred by an alternative PBP (PBP2a/2′) with low affinity for most β-lactam antibiotics. PBP2a is encoded by mecA, which is carried on a mobile genetic element known as SCCmec. A variant of mecA, mecC, was described in 2011 and has been found in Staphylococcus aureus from humans and a wide range of animal species as well as a small number of other staphylococcal species from animals.ObjectivesWe characterized a novel mecC allotype, mecC3, encoded by an environmental isolate of Staphylococcus caeli cultured from air sampling of a commercial rabbit holding.MethodsThe S. caeli isolate 82BT was collected in Italy in 2013 and genome sequenced using MiSeq technology. This allowed the assembly and comparative genomic study of the novel SCCmec region encoding mecC3.ResultsThe study isolate encodes a novel mecA allotype, mecC3, with 92% nucleotide identity to mecC. mecC3 is encoded within a novel SCCmec element distinct from those previously associated with mecC, including a ccrAB pairing (ccrA5B3) not previously linked to mecC.ConclusionsThis is the first description of the novel mecC allotype mecC3, the first isolation of a mecC-positive Staphylococcus in Italy and the first report of mecC in S. caeli. Furthermore, the SCCmec element described here is highly dissimilar to the archetypal SCCmec XI encoding mecC in S. aureus and to elements encoding mecC in other staphylococci. Our report highlights the diversity of mecC allotypes and the diverse staphylococcal species, ecological settings and genomic context in which mecC may be found.

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Associated microflora of medicinal ferns: biotechnological potentials and possible applications

International Journal of Bioassays ◽

10.21746/ijbio.2016.03.0017 ◽

2016 ◽

Vol 5 (03) ◽

pp. 4927 ◽

Cited By ~ 3

Author(s):

Shubhi Srivastava ◽

Paul A. K.

Keyword(s):

Secondary Metabolites ◽

Growth Promotion ◽

Biological Activities ◽

Hydrolytic Enzymes ◽

In Vitro Production ◽

Wide Range ◽

Negative Effect ◽

Bacteria And Fungi

Plant associated microorganisms that colonize the upper and internal tissues of roots, stems, leaves and flowers of healthy plants without causing any visible harmful or negative effect on their host. Diversity of microbes have been extensively studied in a wide variety of vascular plants and shown to promote plant establishment, growth and development and impart resistance against pathogenic infections. Ferns and their associated microbes have also attracted the attention of the scientific communities as sources of novel bioactive secondary metabolites. The ferns and fern alleles, which are well adapted to diverse environmental conditions, produce various secondary metabolites such as flavonoids, steroids, alkaloids, phenols, triterpenoid compounds, variety of amino acids and fatty acids along with some unique metabolites as adaptive features and are traditionally used for human health and medicine. In this review attention has been focused to prepare a comprehensive account of ethnomedicinal properties of some common ferns and fern alleles. Association of bacteria and fungi in the rhizosphere, phyllosphere and endosphere of these medicinally important ferns and their interaction with the host plant has been emphasized keeping in view their possible biotechnological potentials and applications. The processes of host-microbe interaction leading to establishment and colonization of endophytes are less-well characterized in comparison to rhizospheric and phyllospheric microflora. However, the endophytes are possessing same characteristics as rhizospheric and phyllospheric to stimulate the in vivo synthesis as well as in vitro production of secondary metabolites with a wide range of biological activities such as plant growth promotion by production of phytohormones, siderophores, fixation of nitrogen, and phosphate solubilization. Synthesis of pharmaceutically important products such as anticancer compounds, antioxidants, antimicrobials, antiviral substances and hydrolytic enzymes could be some of the promising areas of research and commercial exploitation.

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Bioprospecting Cryptogams as Potential Source of Unique Biodynamic Phytochemicals with Diverse Pharmaceutical Applications

Cryptogam Biodiversity and Assessment ◽

10.21756/cba.v1i1.10959 ◽

2016 ◽

Vol 1 (1) ◽

Author(s):

Brahma N. Singh ◽

Garima Pandey ◽

Prateeksha ◽

J. Kumar

Keyword(s):

Secondary Metabolites ◽

Higher Plants ◽

New Drugs ◽

Terrestrial Plants ◽

Pharmacological Activities ◽

Therapeutic Drugs ◽

Potential Source ◽

Therapeutic Value ◽

Wide Range ◽

Novel Structures

With the advent of green pharmaceuticals, the secondary metabolites derived from plants have provided numerous leads for the development of a wide range of therapeutic drugs; however the discovery of new drugs with novel structures has declined in the past few years. Cryptogams including lichens, bryophytes, and pteridophytes represent a group of small terrestrial plants that remain relatively untouched in the drug discovery process though some have been used as ethnomedicines by various tribes worldwide. Studies of their secondary metabolites are recent but reveal unique secondary metabolites which are not synthesized by higher plants. These compounds can have the potential to develop more potential herbal drugs for prevention and treatment of diseases The present article . deals with the secondary metabolites and pharmacological activities of cryptogams with an objective to bring them forth as potential source of biodynamic compounds of therapeutic value.

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Reading Beyond the Code

10.1093/oso/9780198794776.001.0001 ◽

2018 ◽

Cited By ~ 6

Keyword(s):

Relevance Theory ◽

Literary Studies ◽

The Novel ◽

Human Communication ◽

Communicative Acts ◽

Face To Face ◽

Code Model ◽

Wide Range ◽

Central Claim

This book explores the value for literary studies of relevance theory, an inferential approach to communication in which the expression and recognition of intentions plays a major role. Drawing on a wide range of examples from lyric poetry and the novel, nine of the ten chapters are written by literary specialists and use relevance theory both as an overall framework and as a resource for detailed analysis. The final chapter, written by the co-founder of relevance theory, reviews the issues addressed by the volume and explores their implications for cognitive theories of how communicative acts are interpreted in context. Originally designed to explain how people understand each other in everyday face-to-face exchanges, relevance theory—described in an early review by a literary scholar as ‘the makings of a radically new theory of communication, the first since Aristotle’s’—sheds light on the whole spectrum of human modes of communication, including literature in the broadest sense. Reading Beyond the Code is unique in using relevance theory as a prime resource for literary study, and is also the first to apply the model to a range of phenomena widely seen as supporting an ‘embodied’ conception of cognition and language where sensorimotor processes play a key role. This broadened perspective serves to enhance the value for literary studies of the central claim of relevance theory: that the ‘code model’ is fundamentally inadequate to account for human communication, and in particular for the modes of communication that are proper to literature.

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Genetic, lifestyle, and health-related characteristics of adults without celiac disease who follow a gluten-free diet: a population-based study of 124,447 participants

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa291 ◽

2020 ◽

Author(s):

Thomas J Littlejohns ◽

Amanda Y Chong ◽

Naomi E Allen ◽

Matthew Arnold ◽

Kathryn E Bradbury ◽

...

Keyword(s):

Celiac Disease ◽

Genome Wide Association Study ◽

Population Based ◽

Gluten Free Diet ◽

Hospital Inpatient ◽

Gluten Free ◽

A Genome ◽

Wide Range ◽

Health Related ◽

Reported Health

ABSTRACT Background The number of gluten-free diet followers without celiac disease (CD) is increasing. However, little is known about the characteristics of these individuals. Objectives We address this issue by investigating a wide range of genetic and phenotypic characteristics in association with following a gluten-free diet. Methods The cross-sectional association between lifestyle and health-related characteristics and following a gluten-free diet was investigated in 124,447 women and men aged 40–69 y from the population-based UK Biobank study. A genome-wide association study (GWAS) of following a gluten-free diet was performed. Results A total of 1776 (1.4%) participants reported following a gluten-free diet. Gluten-free diet followers were more likely to be women, nonwhite, highly educated, living in more socioeconomically deprived areas, former smokers, have lost weight in the past year, have poorer self-reported health, and have made dietary changes as a result of illness. Conversely, these individuals were less likely to consume alcohol daily, be overweight or obese, have hypertension, or use cholesterol-lowering medication. Participants with hospital inpatient diagnosed blood and immune mechanism disorders (OR: 1.62; 95% CI: 1.18, 2.21) and non-CD digestive system diseases (OR: 1.58; 95% CI: 1.42, 1.77) were more likely to follow a gluten-free diet. The GWAS demonstrated that no genetic variants were associated with being a gluten-free diet follower. Conclusions Gluten-free diet followers have a better cardiovascular risk profile than non-gluten-free diet followers but poorer self-reported health and a higher prevalence of blood and immune disorders and digestive conditions. Reasons for following a gluten-free diet warrant further investigation.

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A genome-scale metabolic model of Saccharomyces cerevisiae that integrates expression constraints and reaction thermodynamics

Nature Communications ◽

10.1038/s41467-021-25158-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Omid Oftadeh ◽

Pierre Salvy ◽

Maria Masid ◽

Maxime Curvat ◽

Ljubisa Miskovic ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Expression System ◽

Biomass Composition ◽

Industrial Biotechnology ◽

Overflow Metabolism ◽

Cellular Expression ◽

A Genome ◽

Wide Range ◽

Eukaryotic Organisms ◽

Genome Scale

AbstractEukaryotic organisms play an important role in industrial biotechnology, from the production of fuels and commodity chemicals to therapeutic proteins. To optimize these industrial systems, a mathematical approach can be used to integrate the description of multiple biological networks into a single model for cell analysis and engineering. One of the most accurate models of biological systems include Expression and Thermodynamics FLux (ETFL), which efficiently integrates RNA and protein synthesis with traditional genome-scale metabolic models. However, ETFL is so far only applicable for E. coli. To adapt this model for Saccharomyces cerevisiae, we developed yETFL, in which we augmented the original formulation with additional considerations for biomass composition, the compartmentalized cellular expression system, and the energetic costs of biological processes. We demonstrated the ability of yETFL to predict maximum growth rate, essential genes, and the phenotype of overflow metabolism. We envision that the presented formulation can be extended to a wide range of eukaryotic organisms to the benefit of academic and industrial research.

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ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

Human Genomics ◽

10.1186/s40246-021-00304-9 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Sally Badawi ◽

Bassam R. Ali

Keyword(s):

Cell Surface ◽

Angiotensin Converting Enzyme ◽

The Novel ◽

Converting Enzyme ◽

Post Translational Modifications ◽

Angiotensin Converting Enzyme 2 ◽

Viral Attachment ◽

Novel Coronavirus ◽

Effective Medication ◽

Potential Use

AbstractWith the emergence of the novel coronavirus SARS-CoV-2 since December 2019, more than 65 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases, leading to over 1.5 million deaths globally. Despite the collaborative and concerted research efforts that have been made, no effective medication for COVID-19 (coronavirus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in the human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to tackle the virus through the use of angiotensin-converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2, which does not directly aim to reduce its membrane availability. However, through this review, we present a different perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, and shedding and cellular trafficking pathways including the internalization are not well elucidated in literature. Therefore, we hereby present an overview of the fate of newly synthesized ACE2, its post translational modifications, and what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Moreover, an extensive understanding of these processes is necessarily required to evaluate the potential use of ACE2 as a credible therapeutic target.

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