Advances and Applications in Bioinformatics and Chemistry最新文献

{"title":"Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities.","authors":"Bruno O Villoutreix, Rajagopal Krishnamoorthy, Ryad Tamouza, Marion Leboyer, Philippe Beaune","doi":"10.2147/AABC.S304649","DOIUrl":"https://doi.org/10.2147/AABC.S304649","url":null,"abstract":"Introduction There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Objective Based upon clinical observations, we proposed that some psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection. This observation is investigated in the light of experimental in vitro data on SARS-CoV-2. Methods SARS-CoV-2 high-throughput screening results are available at the NCATS COVID-19 portal. We investigated the in vitro anti-viral activity of many psychotropic and antihistaminic drugs using chemoinformatics approaches. Results and Discussion We analyze our clinical observations in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could be used as prophylactic drugs. Other cationic amphiphilic drugs used in other disease areas are also highlighted. Recent analyses of patient electronic health records reported by several research groups indicate that some of these molecules could be of interest at different stages of the disease progression. In addition, recently reported drug combination studies further suggest that it might be valuable to associate several cationic amphiphilic drugs. Taken together, these observations underline the need for clinical trials to fully evaluate the potentials of these molecules, some fitting in the so-called category of broad-spectrum antiviral agents. Repositioning orally available drugs that have moderate side effects and should act on molecular mechanisms less prone to drug resistance would indeed be of utmost importance to deal with COVID-19.","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"14 ","pages":"71-85"},"PeriodicalIF":0.0,"publicationDate":"2021-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/29/aabc-14-71.PMC8051956.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38893742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Understanding of Molecular Interactions and Function Underlying Pain Processes Through Networks of Transcript Isoforms, Genes, and Gene Families.","authors":"Pan Zhang,&nbsp;Bruce R Southey,&nbsp;Jonathan V Sweedler,&nbsp;Amynah Pradhan,&nbsp;Sandra L Rodriguez-Zas","doi":"10.2147/AABC.S284986","DOIUrl":"https://doi.org/10.2147/AABC.S284986","url":null,"abstract":"<p><strong>Introduction: </strong>Molecular networks based on the abundance of mRNA at the gene level and pathway networks that relate families or groups of paralog genes have supported the understanding of interactions between molecules. However, multiple molecular mechanisms underlying health and behavior, such as pain signal processing, are modulated by the abundances of the transcript isoforms that originate from alternative splicing, in addition to gene abundances. Alternative splice variants of growth factors, ion channels, and G-protein-coupled receptors can code for proteoforms that can have different effects on pain and nociception. Therefore, networks inferred using abundance from more agglomerative molecular units (eg, gene family, or gene) have limitations in capturing interactions at a more granular level (eg, gene, or transcript isoform, respectively) do not account for changes in the abundance at the transcript isoform level.</p><p><strong>Objective: </strong>The objective of this study was to evaluate the relative benefits of network inference using abundance patterns at various aggregate levels.</p><p><strong>Methods: </strong>Sparse networks were inferred using Gaussian Markov random fields and a novel aggregation criterion was used to aggregate network edges. The relative advantages of network aggregation were evaluated on two molecular systems that have different dimensions and connectivity, circadian rhythm and Toll-like receptor pathways, using RNA-sequencing data from mice representing two pain level groups, opioid-induced hyperalgesia and control, and two central nervous system regions, the nucleus accumbens and the trigeminal ganglia.</p><p><strong>Results: </strong>The inferred networks were benchmarked against the Kyoto Encyclopedia of Genes and Genomes reference pathways using multiple criteria. Networks inferred using more granular information performed better than networks inferred using more aggregate information. The advantage of granular inference varied with the pathway and data set used.</p><p><strong>Discussion: </strong>The differences in inferred network structure between data sets highlight the differences in OIH effect between central nervous system regions. Our findings suggest that inference of networks using alternative splicing variants can offer complementary insights into the relationship between genes and gene paralog groups.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"14 ","pages":"49-69"},"PeriodicalIF":0.0,"publicationDate":"2021-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7c/d6/aabc-14-49.PMC7901473.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25407578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview of Current Uses and Future Opportunities for Computer-Assisted Design of Vaccines for Neglected Tropical Diseases.","authors":"Raquel Robleda-Castillo,&nbsp;Albert Ros-Lucas,&nbsp;Nieves Martinez-Peinado,&nbsp;Julio Alonso-Padilla","doi":"10.2147/AABC.S258759","DOIUrl":"https://doi.org/10.2147/AABC.S258759","url":null,"abstract":"<p><p>Neglected tropical diseases are infectious diseases that impose high morbidity and mortality rates over 1.5 billion people worldwide. Originally restricted to tropical and subtropical regions, changing climate conditions have increased their potential to emerge elsewhere. Control of their impact suffers from shortages like poor epidemiological surveillance or irregular drug distribution, and some NTDs still lack of appropriate diagnostics and/or efficient therapeutics. For these, availability of vaccines to prevent new infections, or the worsening of those already established, would mean a major breakthrough. However, only dengue and rabies count with approved vaccines at present. Herein, we review the state-of-the-art of vaccination strategies for NTDs, setting the focus on third generation vaccines and the concept of reverse vaccinology. Its capability to address pathogens´ biological complexity, likely contributing to save developmental costs is discussed. The use of computational tools is a fundamental aid to analyze increasingly large datasets aimed at designing vaccine candidates with the highest, possibly, opportunities to succeed. Ultimately, we identify and analyze those studies that took an in silico approach to find vaccine candidates, and experimentally assessed their immunogenicity and/or protection capabilities.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"14 ","pages":"25-47"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ce/69/aabc-14-25.PMC7894434.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25397440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of <i>Clausena anisata</i>: A Potent Inhibitor for Quorum Sensing.","authors":"Rajalakshmanan Eswaramoorthy,&nbsp;Hadgu Hailekiros,&nbsp;Fedlu Kedir,&nbsp;Milkyas Endale","doi":"10.2147/AABC.S290912","DOIUrl":"https://doi.org/10.2147/AABC.S290912","url":null,"abstract":"<p><strong>Introduction: </strong>In modern drug design, in silico methods are largely used to understand drug-receptor interactions and quantum chemical properties. In the present study, a computational de novo design approach was used to confirm mode of binding for antibacterial activity, elucidating quantum chemical properties and ADMET-drug-likeness of carbazole alkaloid (<b>1</b>) and three coumarins (<b>2</b>-<b>4</b>) isolated from roots of <i>Clausena anisata</i>.</p><p><strong>Methods: </strong>Docking studies were performed with DNA-Gyrase (6F86) and LasR binding domain (2UV0) employing a flexible ligand docking approach using AutoDock Vina. SwissADME prediction and toxicological predictions were performed by ADMET. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels.</p><p><strong>Results and discussion: </strong>The docking results revealed that compound <b>3</b> showed better docking scores against both DNA gyrase B and LasR binding domain compared with ciprofloxacin with potential as an inhibitor of bacterial DNA gyrase and quorum sensing LasR binding domain. The SwissADME prediction results showed that all the isolated compounds (<b>1-4</b>) satisfy Lipinski's rule of five with zero violations. Toxicological prediction results suggested that all compounds and ciprofloxacin are non-hepatotoxic, non-carcinogenic, non-irritant, immunogenic, and non-cytotoxic. The DFT analysis results revealed that compound <b>3</b> has large electronegativity (χeV), global softness (σ eV^-1), global electrophilicity (ωeV), and mutagenicity value closer to ciprofloxacin (with LD₅₀ value of 480 mg/kg) suggesting better bioactivity and chemical reactivity with considerable intra-molecular charge transfer between electron-donor to electron-acceptor groups.</p><p><strong>Conclusion: </strong>Overall, compound <b>3</b> may serve as a lead molecule that could be developed into a potent <i>E. coli</i> DNA gyrase B inhibitor and efficient inhibitor for quorum sensing auto-inducer LasR binding domain of <i>Pseudomonas aeruginosa</i>.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"14 ","pages":"13-24"},"PeriodicalIF":0.0,"publicationDate":"2021-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/ee/aabc-14-13.PMC7875078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25370906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome Analysis of <i>Pseudomonas aeruginosa</i> Biofilm Following the Exposure to Malaysian Stingless Bee Honey.","authors":"Nesrin Seder,&nbsp;Mohd Hilmi Abu Bakar,&nbsp;Walid Salem Abu Rayyan","doi":"10.2147/AABC.S292143","DOIUrl":"https://doi.org/10.2147/AABC.S292143","url":null,"abstract":"<p><strong>Introduction: </strong>Malaysian stingless bee honey (<i>Trigona</i>) has been aroused as a potential antimicrobial compound with antibiofilm activity. The capability of the gram-negative bacillus <i>P. aeruginosa</i> to sustain a fatal infection is encoded in the bacterium genome.</p><p><strong>Methods: </strong>In the current study, a transcriptome investigation was performed to explore the mechanism underlying the biofilm dispersal of <i>P. aeruginosa</i> after the exposure to <i>Trigona</i> honey.</p><p><strong>Results: </strong>Microarray analysis of the <i>Pseudomonas</i> biofilm treated by 20% <i>Trigona</i> honey has revealed a down-regulation of 3478 genes among the 6085 screened genes. Specifically, around 13.5% of the down-regulated genes were biofilm-associated genes. The mapping of the biofilm-associated pathways has shown an ultimate decrease in the expression levels of the D-GMP signaling pathway and diguanylate cyclases (<i>DGCs</i>) genes responsible for c-di-GMP formation.</p><p><strong>Conclusion: </strong>We predominantly report the lowering of c-di-GMP through the down-regulation of <i>DGC</i> genes as the main mechanism of biofilm inhibition by <i>Trigona</i> honey.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"14 ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2021-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/5b/aabc-14-1.PMC7814656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38774423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a Kinase-Specific Target Selection Method Using a Structure-Based Machine Learning Approach.","authors":"Arina Afanasyeva,&nbsp;Chioko Nagao,&nbsp;Kenji Mizuguchi","doi":"10.2147/AABC.S278900","DOIUrl":"https://doi.org/10.2147/AABC.S278900","url":null,"abstract":"<p><strong>Introduction: </strong>Despite recent advances in the drug discovery field, developing selective kinase inhibitors remains a complicated issue for a number of reasons, one of which is that there are striking structural similarities in the ATP-binding pockets of kinases.</p><p><strong>Objective: </strong>To address this problem, we have designed a machine learning model utilizing various structure-based and energy-based descriptors to better characterize protein-ligand interactions.</p><p><strong>Methods: </strong>In this work, we use a dataset of 104 human kinases with available PDB structures and experimental activity data against 1202 small-molecule compounds from the PubChem BioAssay dataset \"Navigating the Kinome\". We propose structure-based interaction descriptors to build activity predicting machine learning model.</p><p><strong>Results and discussion: </strong>We report a ligand-oriented computational method for accurate kinase target prioritizing. Our method shows high accuracy compared to similar structure-based activity prediction methods, and more importantly shows the same prediction accuracy when tested on the special set of structurally remote compounds, showing that it is unbiased to ligand structural similarity in the training set data. We hope that our approach will be useful for the development of novel highly selective kinase inhibitors.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"13 ","pages":"27-40"},"PeriodicalIF":0.0,"publicationDate":"2020-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S278900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38689631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics study to improve the substrate adsorption of <i>Saccharomycopsis fibuligera</i> R64 alpha-amylase by designing a new surface binding site.","authors":"Umi Baroroh,&nbsp;Muhammad Yusuf,&nbsp;Saadah Diana Rachman,&nbsp;Safri Ishmayana,&nbsp;Khomaini Hasan,&nbsp;Toto Subroto","doi":"10.2147/AABC.S198110","DOIUrl":"https://doi.org/10.2147/AABC.S198110","url":null,"abstract":"<p><p><b>Background:</b> Carbohydrate binding module (CBM) and surface binding site (SBS) are two important parts of amylase which respond to the raw starch digestion. They are related to the enzyme ability to adsorb and to catalyze the starch hydrolysis. However, starch processing is still expensive due to the high temperature in the gelatinization step. Therefore, direct starch digestion is more favorable. One of the solutions is to use α-amylase with high starch adsorptivity, which is expected to be capable of digesting starch below the gelatinization temperature. In Indonesia, <i>Saccharomycopsis fibuligera</i> R64 α-amylase (Sfamy R64) is one of the enzymes with the highest activity on starch. However, its raw starch adsorptivity was low. The aim of this study was to propose an in-silico model of Sfamy R64 mutant by introducing a new SBS using molecular dynamics (MD) simulation. <b>Methods:</b> The structural behavior of Sfamy R64 and positive control were studied using MD simulation. Furthermore, the mutants of Sfamy R64 were designed to have a stable SBS which mimics the positive control. The substrate affinity in all systems was evaluated using the molecular mechanics generalized Born surface area (MM/GBSA) method. <b>Results:</b> The stability of a new SBS constructed by seven substitutions and a loop insertion was improved throughout MD simulation. The substrate was consistently bound to the SBS over 55 ns of simulation, as compared to 14 ns in wild-type. The structural behavior of SBS in mutant and positive control was similar. The interaction energies of the positive control, wild-type, and mutant were -17.6, -5.2, and -8.2 kcal/mol, respectively. <b>Conclusion:</b> The enhanced substrate binding in the mutant, due to the existence of a new SBS, suggests the potential of improving starch adsorptivity of Sfamy R64. This result should be useful in developing an enzyme with better substrate adsorption based on the rational computer-aided molecular design approach.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"12 ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2019-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S198110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37361454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prioritizing single-nucleotide polymorphisms and variants associated with clinical mastitis.","authors":"Prashanth Suravajhala,&nbsp;Alfredo Benso","doi":"10.2147/AABC.S123604","DOIUrl":"https://doi.org/10.2147/AABC.S123604","url":null,"abstract":"<p><p>Next-generation sequencing technology has provided resources to easily explore and identify candidate single-nucleotide polymorphisms (SNPs) and variants. However, there remains a challenge in identifying and inferring the causal SNPs from sequence data. A problem with different methods that predict the effect of mutations is that they produce false positives. In this hypothesis, we provide an overview of methods known for identifying causal variants and discuss the challenges, fallacies, and prospects in discerning candidate SNPs. We then propose a three-point classification strategy, which could be an additional annotation method in identifying causalities.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"10 ","pages":"57-64"},"PeriodicalIF":0.0,"publicationDate":"2017-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S123604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35120526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The identification of protein domains that mediate functional interactions between Rab-GTPases and RabGAPs using 3D protein modeling.","authors":"Jeremiah J Davie,&nbsp;Silviu L Faitar","doi":"10.2147/AABC.S121245","DOIUrl":"https://doi.org/10.2147/AABC.S121245","url":null,"abstract":"<p><p>Currently, time-consuming serial in vitro experimentation involving immunocytochemistry or radiolabeled materials is required to identify which of the numerous Rab-GTPases (Rab) and Rab-GTPase activating proteins (RabGAP) are capable of functional interactions. These interactions are essential for numerous cellular functions, and in silico methods of reducing in vitro trial and error would accelerate the pace of research in cell biology. We have utilized a combination of three-dimensional protein modeling and protein bioinformatics to identify domains present in Rab proteins that are predictive of their functional interaction with a specific RabGAP. The RabF2 and RabSF1 domains appear to play functional roles in mediating the interaction between Rabs and RabGAPs. Moreover, the RabSF1 domain can be used to make in silico predictions of functional Rab/RabGAP pairs. This method is expected to be a broadly applicable tool for predicting protein-protein interactions where existing crystal structures for homologs of the proteins of interest are available.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"10 ","pages":"47-56"},"PeriodicalIF":0.0,"publicationDate":"2017-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S121245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34935480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic interrelations in the actinomycin biosynthetic gene clusters of <i>Streptomyces antibioticus</i> IMRU 3720 and <i>Streptomyces chrysomallus</i> ATCC11523, producers of actinomycin X and actinomycin C.","authors":"Ivana Crnovčić,&nbsp;Christian Rückert,&nbsp;Siamak Semsary,&nbsp;Manuel Lang,&nbsp;Jörn Kalinowski,&nbsp;Ullrich Keller","doi":"10.2147/AABC.S117707","DOIUrl":"https://doi.org/10.2147/AABC.S117707","url":null,"abstract":"<p><p>Sequencing the actinomycin (<i>acm</i>) biosynthetic gene cluster of <i>Streptomyces antibioticus</i> IMRU 3720, which produces actinomycin X (Acm X), revealed 20 genes organized into a highly similar framework as in the bi-armed <i>acm</i> C biosynthetic gene cluster of <i>Streptomyces chrysomallus</i> but without an attached additional extra arm of orthologues as in the latter. Curiously, the extra arm of the <i>S. chrysomallus</i> gene cluster turned out to perfectly match the single arm of the <i>S. antibioticus</i> gene cluster in the same order of orthologues including the the presence of two pseudogenes, <i>scacmM</i> and <i>scacmN</i>, encoding a cytochrome P450 and its ferredoxin, respectively. Orthologues of the latter genes were both missing in the principal arm of the <i>S. chrysomallus acm</i> C gene cluster. All orthologues of the extra arm showed a G +C-contents different from that of their counterparts in the principal arm. Moreover, the similarities of translation products from the extra arm were all higher to the corresponding translation products of orthologue genes from the <i>S. antibioticus acm X</i> gene cluster than to those encoded by the principal arm of their own gene cluster. This suggests that the duplicated structure of the <i>S. chrysomallus acm</i> C biosynthetic gene cluster evolved from previous fusion between two one-armed <i>acm</i> gene clusters each from a different genetic background. However, while <i>scacmM</i> and <i>scacmN</i> in the extra arm of the <i>S. chrysomallus acm</i> C gene cluster are mutated and therefore are non-functional, their orthologues <i>saacmM</i> and <i>saacmN</i> in the <i>S. antibioticus acm</i> C gene cluster show no defects seemingly encoding active enzymes with functions specific for Acm X biosynthesis. Both <i>acm</i> biosynthetic gene clusters lack a kynurenine-3-monooxygenase gene necessary for biosynthesis of 3-hydroxy-4-methylanthranilic acid, the building block of the Acm chromophore, which suggests participation of a genome-encoded relevant monooxygenase during Acm biosynthesis in both <i>S. chrysomallus</i> and <i>S. antibioticus</i>.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"10 ","pages":"29-46"},"PeriodicalIF":0.0,"publicationDate":"2017-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S117707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34935479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}