ORCID Profile
0000-0003-2571-6016
Current Organisation
University Of Strathclyde
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Publisher: Cold Spring Harbor Laboratory
Date: 20-05-2020
DOI: 10.1101/2020.05.20.105536
Abstract: Actinobacteria are a large and erse phylum of bacteria that contains medically and ecologically relevant organisms. Many members are valuable sources of bioactive natural products and chemical precursors that are exploited in the clinic. These are made using the enzyme pathways encoded in their complex genomes. Whilst the number of sequenced genomes has increased rapidly in the last twenty years, the large size and complexity of many Actinobacterial genomes means that the sequences remain incomplete and consist of large numbers of contigs with poor annotation, which hinders large scale comparative genomics and evolutionary studies. To enable greater understanding and exploitation of Actinobacterial genomes, specialist genomic databases must be linked to high-quality genome sequences. Here we provide a curated database of 612 high-quality actinobacterial genomes from 80 genera, chosen to represent a broad phylogenetic group with equivalent genome reannotation. Utilising this database will provide researchers with a framework for evolutionary and metabolic studies, to enable a foundation for genome and metabolic engineering, to facilitate discovery of novel bioactive therapeutics and studies on gene family evolution. The Actinobacteria are a large erse phylum of bacteria, often with large, complex genomes with a high G+C content. Sequence databases have great variation in the quality of sequences, equivalence of annotation and phylogenetic representation, which makes it challenging to undertake evolutionary and phylogenetic studies. To address this, we have assembled a curated, taxa-specific, non-redundant database to aid detailed comparative analysis of Actinobacteria. ActDES constitutes a novel resource for the community of Actinobacterial researchers that will be useful primarily for two types of analyses: (i) comparative genomic studies – facilitated by reliable identification of orthologs across a set of defined, phylogenetically-representative genomes, and (ii) phylogenomic studies which will be improved by identification of gene subsets at specified taxonomic level. These analyses can then act as a springboard for the studies of the evolution of virulence genes, the evolution of metabolism and identification of targets for metabolic engineering. All genome sequences used in this study can be found in the NCBI taxonomy browser www.ncbi.nlm.nih.gov/Taxonomy/Browser/www.tax.cgi and are summarised along with Accession numbers in Table S1 All other data are available on Figshare 0.6084/m9.figshare.12167529 and 0.5281/zenodo.3830391 Perl script files available on GitHub selem/ActDES including details of how to batch annotate genomes in RAST from the terminal selem/myrast Supp. Table S1 List of genomes from NCBI (Actinobacteria database.xlsx) 0.6084/m9.figshare.12167529 CVS genome annotation files including the FASTA files of nucleotide and amino acids sequences (in idual .cvs files) 0.6084/m9.figshare.12167880 BLAST nucleotide database (.fasta file) 0.6084/m9.figshare.12167724 BLAST protein database (.fasta file) 0.6084/m9.figshare.12167724 Supp. Table S2 Expansion table genus level (Expansion table.xlsx Tab Genus level) 0.6084/m9.figshare.12167529 Supp. Table S2 Expansion table species level (Expansion table.xlsx Tab species level) 0.6084/m9.figshare.12167529 All GlcP and Glk data – blast hits from ActDES database, MUSCLE Alignment files and .nwk tree files can be found at 0.6084/m9.figshare.12167529 Interactive trees in Microreact for Glk tree roject/w_KDfn1xA/90e6759e and associated files can be found at 0.6084/m9.figshare.12326441.v1 Interactive trees in Microreact for GlcP tree roject/VBUdiQ5_k/0fc4622b and associated files can be found at 0.6084/m9.figshare.12326441.v1
Publisher: American Society for Microbiology
Date: 07-03-2018
Abstract: The expansion of the genetic repertoire of an organism by gene duplication or horizontal gene transfer (HGT) can aid adaptation. Streptomyces bacteria are prolific producers of bioactive specialized metabolites that have adaptive functions in nature and have found extensive utility in human medicine. While the biosynthesis of these specialized metabolites is directed by dedicated biosynthetic gene clusters, little attention has been focused on how these organisms have evolved robustness in their genomes to facilitate the metabolic plasticity required to provide chemical precursors for biosynthesis during the complex metabolic transitions from vegetative growth to specialized metabolite production and sporulation. Here, we examine genetic redundancy in actinobacteria and show that specialized metabolite-producing bacterial families exhibit gene family expansion in primary metabolism. Focusing on a gene duplication event, we show that the two pyruvate kinases in the genome of Streptomyces coelicolor arose by an ancient duplication event and that each has evolved altered enzymatic kinetics, with Pyk1 having a 20-fold-higher k cat than Pyk2 (4,703 s −1 compared to 215 s −1 , respectively), and yet both are constitutively expressed. The pyruvate kinase mutants were also found to be compromised in terms of fitness compared to wild-type Streptomyces . These data suggest that expanding gene families can help maintain cell functionality during metabolic perturbation such as nutrient limitation and/or specialized metabolite production. IMPORTANCE The rise of antimicrobial-resistant infections has prompted a resurgence in interest in understanding the production of specialized metabolites, such as antibiotics, by Streptomyces . The presence of multiple genes encoding the same enzymatic function is an aspect of Streptomyces biology that has received little attention however, understanding how the metabolic expansion influences these organisms can help enhance production of clinically useful molecules. Here, we show that expanding the number of pyruvate kinases enables metabolic adaptation, increases strain fitness, and represents an excellent target for metabolic engineering of industrial specialized metabolite-producing bacteria and the activation of cryptic specialized metabolites.
Publisher: Microbiology Society
Date: 2021
Abstract: Actinobacteria is a large and erse phylum of bacteria that contains medically and ecologically relevant organisms. Many members are valuable sources of bioactive natural products and chemical precursors that are exploited in the clinic and made using the enzyme pathways encoded in their complex genomes. Whilst the number of sequenced genomes has increased rapidly in the last 20 years, the large size, complexity and high G+C content of many actinobacterial genomes means that the sequences remain incomplete and consist of large numbers of contigs with poor annotation, which hinders large-scale comparative genomic and evolutionary studies. To enable greater understanding and exploitation of actinobacterial genomes, specialized genomic databases must be linked to high-quality genome sequences. Here, we provide a curated database of 612 high-quality actinobacterial genomes from 80 genera, chosen to represent a broad phylogenetic group with equivalent genome re-annotation. Utilizing this database will provide researchers with a framework for evolutionary and metabolic studies, to enable a foundation for genome and metabolic engineering, to facilitate discovery of novel bioactive therapeutics and studies on gene family evolution. This article contains data hosted by Microreact.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
DOI: 10.1007/S12275-015-5076-6
Abstract: Endophytic bacteria, such as Streptomyces, have the potential to act as a source for novel bioactive molecules with medicinal properties. The present study was aimed at assessing the antimalarial activity of crude extract isolated from various strains of actinobacteria living endophytically in some Malaysian medicinal plants. Using the four day suppression test method on male ICR strain mice, compounds produced from three strains of Streptomyces (SUK8, SUK10, and SUK27) were tested in vivo against Plasmodium berghei PZZ1/100 in an antimalarial screen using crude extracts at four different concentrations. One of these extracts, isolated from Streptomyces SUK10 obtained from the bark of Shorea ovalis tree, showed inhibition of the test organism and was further tested against P. berghei-infected mice for antimalarial activity at different concentrations. There was a positive relationship between the survival of the infected mouse group treated with 50 µg/kg body weight (bw) of ethyl acetate-SUK10 crude extract and the ability to inhibit the parasites growth. The parasite inhibition percentage for this group showed that 50% of the mice survived for more than 90 days after infection with the parasite. The nucleotide sequence and phylogenetic tree suggested that Streptomyces SUK10 may constitute a new species within the Streptomyces genus. As part of the drug discovery process, these promising finding may contribute to the medicinal and pharmaceutical field for malarial treatment.
Publisher: Wiley
Date: 30-08-2012
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Iain Hunter.