ORCID Profile
0000-0002-6751-8897
Current Organisations
University of California, Berkeley
,
Instituto Tecnologico de Estudios Superiores de Monterrey
,
DTU Biosustain, The Novo Nordisk Foundation Center for Biosustainability
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Publications
ActDES – a Curated Actinobacterial Database for Evolutionary Studies
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
Systems Biology Approaches to Understand Natural Products Biosynthesis
Publisher: Frontiers Media SA
Date: 09-12-2015
First Draft Genome Sequence of a Strain from the Genus Citricoccus
Publisher: American Society for Microbiology
Date: 11-2011
DOI: 10.1128/JB.06045-11
Abstract: Bacteria of the genus Citricoccus have been isolated from ecological niches characterized by erse abiotic stress conditions. Here we report the first genome draft of a strain of the genus Citricoccus isolated from the extremely oligotrophic Churince system in the Cuatro Ciénegas Basin (CCB) in Coahuila, Mexico.
Phylogenomic Analysis of Natural Products Biosynthetic Gene Clusters Allows Discovery of Arseno-Organic Metabolites in Model Streptomycetes
Publisher: Oxford University Press (OUP)
Date: 06-2016
DOI: 10.1093/GBE/EVW125
ActDES – a curated Actinobacterial Database for Evolutionary Studies
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.
Revisiting the evolution and taxonomy of Clostridia, a phylogenomic update
Publisher: Cold Spring Harbor Laboratory
Date: 11-02-2019
DOI: 10.1101/546341
Abstract: Clostridium is a large genus of obligate anaerobes belonging to the Firmicutes phylum of bacteria, most of which have a Gram-positive cell wall structure. The genus includes significant human and animal pathogens, causative of potentially deadly diseases such as tetanus and botulism. Despite their relevance and many studies suggesting that they are not a monophyletic group, the taxonomy of the group has largely been neglected. Currently, species belonging to the genus are placed in the unnatural order defined as Clostridiales , which includes the class Clostridia . Here we used genomic data from 779 strains to study the taxonomy and evolution of the group. This analysis allowed us to (i) confirm that the group is composed of more than one genus (ii), detect major differences between pathogens classified as a single species within the group of authentic Clostridium spp. ( sensu stricto ), identify inconsistencies between taxonomy and toxin evolution that reflect on the pervasive misclassification of strains and, (iv) identify differential traits within central metabolism of members of what has been defined earlier and confirmed by us as cluster I. Our analysis shows that the current taxonomic classification of Clostridium species hinders the prediction of functions and traits, suggests a new classification for this fascinating class of bacteria and highlights the importance of phylogenomics for taxonomic studies.
Revisiting the Evolution and Taxonomy of Clostridia, a Phylogenomic Update
Publisher: Oxford University Press (OUP)
Date: 10-05-2019
DOI: 10.1093/GBE/EVZ096
Abstract: Clostridium is a large genus of obligate anaerobes belonging to the Firmicutes phylum of bacteria, most of which have a Gram-positive cell wall structure. The genus includes significant human and animal pathogens, causative of potentially deadly diseases such as tetanus and botulism. Despite their relevance and many studies suggesting that they are not a monophyletic group, the taxonomy of the group has largely been neglected. Currently, species belonging to the genus are placed in the unnatural order defined as Clostridiales, which includes the class Clostridia. Here, we used genomic data from 779 strains to study the taxonomy and evolution of the group. This analysis allowed us to 1) confirm that the group is composed of more than one genus, 2) detect major differences between pathogens classified as a single species within the group of authentic Clostridium spp. (sensu stricto), 3) identify inconsistencies between taxonomy and toxin evolution that reflect on the pervasive misclassification of strains, and 4) identify differential traits within central metabolism of members of what has been defined earlier and confirmed by us as cluster I. Our analysis shows that the current taxonomic classification of Clostridium species hinders the prediction of functions and traits, suggests a new classification for this fascinating class of bacteria, and highlights the importance of phylogenomics for taxonomic studies.
Synthetic biology of avermectin for production improvement and structure diversification
Publisher: Wiley
Date: 29-01-2014
Abstract: Natural products are still key sources of current clinical drugs and innovative therapeutic agents. Since wild-type microorganisms only produce natural products in very small quantities, yields of production strains need to be improved by breaking down the precise genetic and biochemical circuitry. Herein, we use avermectins as an ex le of production improvement and chemical structure ersification by synthetic biology. Avermectins are macrocyclic lactones produced by Streptomyces avermitilis and are well known and widely used for antiparasitic therapy. Given the importance of this molecule and its derivatives, many efforts and strategies were employed to improve avermectin production and generate new active analogues. This review describes the current status of synthetic strategies successfully applied for developing natural-product-producing strains and discusses future prospects for the application of enhanced avermectin production.
Cycad Coralloid Roots Contain Bacterial Communities Including Cyanobacteria andCaulobacterspp. That Encode Niche-Specific Biosynthetic Gene Clusters
Publisher: Oxford University Press (OUP)
Date: 11-12-2018
DOI: 10.1093/GBE/EVY266
Inter-Kingdom beach warfare: Microbial chemical communication activates natural chemical defences
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
What can genome-scale metabolic network reconstructions do for prokaryotic systematics?
Publisher: Springer Science and Business Media LLC
Date: 21-10-2011
DOI: 10.1007/S10482-011-9655-1
Abstract: It has recently been proposed that in addition to Nomenclature, Classification and Identification, Comprehending Microbial Diversity may be considered as the fourth tenet of microbial systematics [Staley JT (2010) The Bulletin of BISMiS, 1(1): 1-5]. As this fourth goal implies a fundamental understanding of microbial speciation, this perspective article argues that translation of bacterial genome sequences into metabolic features may contribute to the development of modern polyphasic taxonomic approaches. Genome-scale metabolic network reconstructions (GSMRs), which are the result of computationally predicted and experimentally confirmed stoichiometric matrices incorporating all enzyme and metabolite components encoded by a genome sequence, provide a platform that can illustrate bacterial speciation. As the topology and the composition of GSMRs are expected to be the result of adaptive evolution, the features of these networks may provide the prokaryotic taxonomist with novel tools for reaching the fourth tenet of microbial systematics. Through selected ex les from the Actinobacteria, which have been inferred from GSMRs and experimentally confirmed after phenotypic characterisation, it will be shown that this level of information can be incorporated into modern polyphasic taxonomic approaches. In conclusion, three specific ex les are illustrated to show how GSMRs will revolutionize prokaryotic systematics, as has previously occurred in many other fields of microbiology.
Biofuels for a sustainable future
Publisher: Elsevier BV
Date: 03-2021
Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in Streptomyces
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.
Talaropeptides A-D: Structure and Biosynthesis of Extensively N-methylated Linear Peptides From an Australian Marine Tunicate-Derived Talaromyces sp.
Publisher: Frontiers Media SA
Date: 04-09-2018
A computational framework to explore large-scale biosynthetic diversity
Publisher: Springer Science and Business Media LLC
Date: 25-11-2019
Diverse Cone-Snail Species Harbor Closely Related Streptomyces Species with Conserved Chemical and Genetic Profiles, Including Polycyclic Tetramic Acid Macrolactams
Publisher: Frontiers Media SA
Date: 24-11-2017
Draft Genome Sequence of Sphingobacterium sp. CZ-UAM, Isolated from a Methanotrophic Consortium
Publisher: American Society for Microbiology
Date: 17-08-2017
Abstract: Sphingobacterium sp. CZ-UAM was isolated from a methanotrophic consortium in mineral medium using methane as the only carbon source. A draft genome of 5.84 Mb with a 40.77% G+C content is reported here. This genome sequence will allow the investigation of potential methanotrophy in this isolated strain.
MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters.
Publisher: Oxford University Press (OUP)
Date: 18-11-2022
DOI: 10.1093/NAR/GKAC1049
Abstract: With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for erse natural products. MIBiG 3.0 is accessible online at
Actinobacteria phylogenomics, selective isolation from an iron oligotrophic environment and siderophore functional characterization, unveil new desferrioxamine traits
Publisher: Oxford University Press (OUP)
Date: 07-07-2017
Related Organisations
E O Lawrence Berkeley National Laboratory
Location: United States of America
University Of California, Berkeley
Location: United States of America
Instituto Tecnologico De Estudios Superiores De Monterrey
Location: Mexico
DTU Biosustain, The Novo Nordisk Foundation Center For Biosustainability
Location: Denmark
Related Funding Activities
No related grants have been discovered for Pablo Cruz-Morales.