scholarly journals Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

2021 ◽  
Author(s):  
Virginia Lioy ◽  
Jean-Noël Lorenzi ◽  
Soumaya Najah ◽  
Thibault Poinsignon ◽  
Leh Hervé ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Chromosome Structure ◽  
Gene Clusters ◽  
Structural Features ◽  
Biosynthetic Gene Clusters ◽  
Linear Chromosome ◽  
Chromosome Architecture ◽  
Specialized Metabolites ◽  
And Function ◽  
Core Genes

Abstract Streptomyces are among the most prolific bacterial producers of specialized metabolites, including antibiotics. The linear chromosome is partitioned into a central region harboring core genes and two extremities enriched in specialized metabolite biosynthetic gene clusters (SMBGCs). The molecular mechanisms governing structure and function of these compartmentalized genomes remain mostly unknown. Here we show that in exponential phase, chromosome structure correlates with genetic compartmentalization: conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends are transcriptionally, largely quiescent compartments with different structural features. Onset of metabolic differentiation is accompanied by remodeling of chromosome architecture from an ‘open’ to a rather ‘closed’ conformation, in which the SMBGCs are expressed forming new boundaries. Altogether, our results reveal that S. ambofaciens’ linear chromosome is partitioned into structurally distinct entities, indicating a link between chromosome folding, gene expression and genome evolution.

scholarly journals Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

2020 ◽  
Author(s):  
Virginia Lioy ◽  
Jean-Noël Lorenzi ◽  
Soumaya Najah ◽  
Thibault Poinsignon ◽  
Hervé Leh ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Chromosome Structure ◽  
Gene Clusters ◽  
Structural Features ◽  
Biosynthetic Gene Clusters ◽  
Linear Chromosome ◽  
Chromosome Architecture ◽  
Specialized Metabolites ◽  
And Function ◽  
Core Genes

AbstractStreptomyces are among the most prolific bacterial producers of specialized metabolites, including antibiotics. The linear chromosome is partitioned into a central region harboring core genes and two extremities enriched in specialized metabolite biosynthetic gene clusters (SMBGCs). The molecular mechanisms governing structure and function of these compartmentalized genomes remain mostly unknown. Here we show that in exponential phase, chromosome structure correlates with genetic compartmentalization: conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends are transcriptionally, largely quiescent compartments with different structural features. Onset of metabolic differentiation is accompanied by remodeling of chromosome architecture from an ‘open’ to a rather ‘closed’ conformation, in which the SMBGCs are expressed forming new boundaries. Altogether, our results reveal that S. ambofaciens’ linear chromosome is partitioned into structurally distinct entities, indicating a link between chromosome folding, gene expression and genome evolution.

scholarly journals Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Virginia S. Lioy ◽  
Jean-Noël Lorenzi ◽  
Soumaya Najah ◽  
Thibault Poinsignon ◽  
Hervé Leh ◽  
...  
Keyword(s):  
Chromosome Structure ◽  
Gene Clusters ◽  
Structural Features ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Linear Chromosome ◽  
Chromosome Architecture ◽  
Specialized Metabolites ◽  
Streptomyces Ambofaciens ◽  
Core Genes

AbstractBacteria of the genus Streptomyces are prolific producers of specialized metabolites, including antibiotics. The linear chromosome includes a central region harboring core genes, as well as extremities enriched in specialized metabolite biosynthetic gene clusters. Here, we show that chromosome structure in Streptomyces ambofaciens correlates with genetic compartmentalization during exponential phase. Conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends tend to be transcriptionally quiescent compartments with different structural features. The onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture, from a rather ‘open’ to a ‘closed’ conformation, in which highly expressed specialized metabolite biosynthetic genes form new boundaries. Thus, our results indicate that the linear chromosome of S. ambofaciens is partitioned into structurally distinct entities, suggesting a link between chromosome folding, gene expression and genome evolution.

scholarly journals Transporter genes in biosynthetic gene clusters predict metabolite characteristics and siderophore activity

2020 ◽  
Author(s):  
Alexander Crits-Christoph ◽  
Nicholas Bhattacharya ◽  
Matthew R. Olm ◽  
Yun S. Song ◽  
Jillian F. Banfield
Keyword(s):  
Gut Microbiome ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Gene Frequencies ◽  
Specialized Metabolites ◽  
Molecular Weights ◽  
And Function ◽  
Extracellular Environment ◽  
Siderophore Activity

AbstractBiosynthetic gene clusters (BGCs) are operonic sets of microbial genes that synthesize specialized metabolites with diverse functions, including siderophores and antibiotics, which often require export to the extracellular environment. For this reason, genes for transport across cellular membranes are essential for the production of specialized metabolites, and are often genomically co-localized with BGCs. Here we conducted a comprehensive computational analysis of transporters associated with characterized BGCs. In addition to known exporters, in BGCs we found many importer-specific transmembrane domains that co-occur with substrate binding proteins possibly for uptake of siderophores or metabolic precursors. Machine learning models using transporter gene frequencies were predictive of known siderophore activity, molecular weights, and a measure of lipophilicity (log P) for corresponding BGC-synthesized metabolites. Transporter genes associated with BGCs were often equally or more predictive of metabolite features than biosynthetic genes. Given the importance of siderophores as pathogenicity factors, we used transporters specific for siderophore BGCs to identify both known and uncharacterized siderophore-like BGCs in genomes from metagenomes from the infant and adult gut microbiome. We find that 23% of microbial genomes from the infant gut have siderophore-like BGCs, but only 3% of those assembled from adult gut microbiomes do. While siderophore-like BGCs from the infant gut are predominantly associated with Enterobactericaee and Staphylococcus, siderophore-like BGCs can be identified from taxa in the adult gut microbiome that have rarely been recognized for siderophore production. Taken together, these results show that consideration of BGC-associated transporter genes can inform predictions of specialized metabolite structure and function.

scholarly journals A global co-expression network approach for connecting genes to specialized metabolic pathways in plants

2016 ◽  
Author(s):  
Jennifer H. Wisecaver ◽  
Alexander T. Borowsky ◽  
Vered Tzin ◽  
Georg Jander ◽  
Daniel J. Kliebenstein ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Meta Analysis ◽  
Null Distribution ◽  
Gene Clusters ◽  
Cytochrome P450s ◽  
Model Organisms ◽  
Biosynthetic Gene Clusters ◽  
Terpene Synthases ◽  
Specialized Metabolites ◽  
Data Source

AbstractPlants produce a tremendous diversity of specialized metabolites (SMs) to interact with and manage their environment. A major challenge hindering efforts to tap this seemingly boundless source of pharmacopeia is the identification of SM pathways and their constituent genes. Given the well-established observation that the genes comprising a SM pathway are co-regulated in response to specific environmental conditions, we hypothesized that genes from a given SM pathway would form tight associations (modules) with each other in gene co-expression networks, facilitating their identification. To evaluate this hypothesis, we used 10 global co-expression datasets—each a meta-analysis of hundreds to thousands of expression experiments—across eight plant model organisms to identify hundreds of modules of co-expressed genes for each species. In support of our hypothesis, 15.3-52.6% of modules contained two or more known SM biosynthetic genes (e.g., cytochrome P450s, terpene synthases, and chalcone synthases), and module genes were enriched in SM functions (e.g., glucoside and flavonoid biosynthesis). Moreover, modules recovered many experimentally validated SM pathways in these plants, including all six known to form biosynthetic gene clusters (BGCs). In contrast, genes predicted based on physical proximity on a chromosome to form plant BGCs were no more co-expressed than the null distribution for neighboring genes. These results not only suggest that most predicted plant BGCs do not represent genuine SM pathways but also argue that BGCs are unlikely to be a hallmark of plant specialized metabolism. We submit that global gene co-expression is a rich, but largely untapped, data source for discovering the genetic basis and architecture of plant natural products, which can be applied even without knowledge of the genome sequence.

scholarly journals tRNA Genes Affect Chromosome Structure and Function via Local Effects

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Omar Hamdani ◽  
Namrita Dhillon ◽  
Tsung-Han S. Hsieh ◽  
Takahiro Fujita ◽  
Josefina Ocampo ◽  
...  
Keyword(s):  
Long Range ◽  
Binding Sites ◽  
Genomic Organization ◽  
Chromosome Structure ◽  
Trna Genes ◽  
Local Effects ◽  
Chromosome Architecture ◽  
Architectural Proteins ◽  
And Function ◽  
Chromosome Tethering

ABSTRACT The genome is packaged and organized in an ordered, nonrandom manner, and specific chromatin segments contact nuclear substructures to mediate this organization. tRNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the roles of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacked any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromatin architecture or chromosome tethering and mobility. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long-range HML-HMR heterochromatin clustering with concomitant effects on gene silencing. We propose that the tDNAs primarily affect local chromatin structure, which results in effects on long-range chromosome architecture.

scholarly journals Complex evolutionary dynamics govern the diversity and distribution of biosynthetic gene clusters and their encoded specialized metabolites

2020 ◽  
Author(s):  
Alexander B. Chase ◽  
Douglas Sweeney ◽  
Mitchell N. Muskat ◽  
Dulce Guillén-Matus ◽  
Paul R. Jensen
Keyword(s):  
Evolutionary Dynamics ◽  
Gene Clusters ◽  
Ecological Interactions ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Evolutionary Processes ◽  
Specialized Metabolites ◽  
Marine Actinomycete ◽  
Species Specific ◽  
Gain Loss

ABSTRACTWhile specialized metabolites are thought to mediate ecological interactions, the evolutionary processes driving their distributions, particularly among closely related lineages, remain poorly understood. Here, we examine the evolutionary dynamics governing the diversity and distribution of biosynthetic gene clusters (BGCs) in 118 strains across nine described species within the marine actinomycete genus Salinispora. While previous evidence indicated that horizontal gene transfer largely contributed to BGC diversity, we find that a majority of BGCs in Salinispora genomes are maintained by processes of vertical descent. In particular, we identified species-specific signatures that were associated with both BGC distributions and the production of their encoded specialized metabolites. By analyzing nine experimentally characterized BGCs that range in conservation from species to genus specific, we find that the distribution of BGCs among Salinispora species is maintained by selection, while BGC diversification is constrained by recombination among closely related strains and strengthened by gain/loss events between species. Notably, the evolutionary processes driving BGC diversification had direct consequences for compound production, elucidating the mechanisms that lead to chemical diversification. These results support the concept that specialized metabolites, and their cognate BGCs, represent functional traits associated with ecological differentiation among Salinispora species.GRAPHICAL ABSTRACT

scholarly journals GRINS: Genetic elements that recode assembly-line polyketide synthases and accelerate their diversification

2021 ◽  
Vol 118 (26) ◽  
pp. e2100751118 ◽  
Author(s):  
Aleksandra Nivina ◽  
Sur Herrera Paredes ◽  
Hunter B. Fraser ◽  
Chaitan Khosla
Keyword(s):  
Molecular Mechanisms ◽  
Assembly Line ◽  
Gene Families ◽  
Gene Clusters ◽  
Nucleotide Composition ◽  
Polyketide Synthases ◽  
Bacterial Genomes ◽  
Biosynthetic Gene Clusters ◽  
Bacterial Phyla ◽  
Genetic Elements

Assembly-line polyketide synthases (PKSs) are large and complex enzymatic machineries with a multimodular architecture, typically encoded in bacterial genomes by biosynthetic gene clusters. Their modularity has led to an astounding diversity of biosynthesized molecules, many with medical relevance. Thus, understanding the mechanisms that drive PKS evolution is fundamental for both functional prediction of natural PKSs as well as for the engineering of novel PKSs. Here, we describe a repetitive genetic element in assembly-line PKS genes which appears to play a role in accelerating the diversification of closely related biosynthetic clusters. We named this element GRINS: genetic repeats of intense nucleotide skews. GRINS appear to recode PKS protein regions with a biased nucleotide composition and to promote gene conversion. GRINS are present in a large number of assembly-line PKS gene clusters and are particularly widespread in the actinobacterial genus Streptomyces. While the molecular mechanisms associated with GRINS appearance, dissemination, and maintenance are unknown, the presence of GRINS in a broad range of bacterial phyla and gene families indicates that these genetic elements could play a fundamental role in protein evolution.

scholarly journals Bagremycin Antibiotics and Ferroverdin iron-chelators are synthetized by the Same Gene Cluster

2019 ◽  
Author(s):  
Loïc Martinet ◽  
Aymeric Naômé ◽  
Benoit Deflandre ◽  
Marta Maciejewska ◽  
Déborah Tellatin ◽  
...  
Keyword(s):  
Environmental Conditions ◽  
Biosynthetic Pathway ◽  
Gene Clusters ◽  
Iron Chelators ◽  
Hydroxybenzoic Acid ◽  
Iron Availability ◽  
Biosynthetic Gene ◽  
Single Family ◽  
Biosynthetic Gene Clusters ◽  
Specialized Metabolites

AbstractBiosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and bagremycins, which are families of metabolites with different bioactivities, are produced from the same BGC, whereby the fate of the biosynthetic pathway depends on iron availability. Under conditions of iron depletion, the monomeric bagremycins are formed, which are amino-aromatic antibiotics resulting from the condensation of 3-amino-4-hydroxybenzoic acid with p-vinylphenol. Conversely, when iron is abundantly available, the biosynthetic pathway additionally produces a molecule based on p-vinylphenyl-3-nitroso-4-hydroxybenzoate, which complexes iron to form the trimeric ferroverdins that have anticholesterol activity. Thus our work challenges the concept that BGCs should produce a single family of molecules with one type of bioactivity, the occurrence of the different metabolites being triggered by the environmental conditions.

scholarly journals Structure and Function of Caltrin (Calcium Transport Inhibitor) Proteins

2017 ◽  
Vol 10 ◽  
pp. 117862641774582
Author(s):  
Ernesto Javier Grasso ◽  
Carlos Enrique Coronel
Keyword(s):  
Intracellular Signaling ◽  
Calcium Transport ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Structural Features ◽  
Female Reproductive Tract ◽  
Sperm Cells ◽  
Transport Inhibitor ◽  
Acrosomal Exocytosis ◽  
And Function

Caltrin (calcium transport inhibitor) is a family of small and basic proteins of the mammalian seminal plasma which bind to sperm cells during ejaculation and inhibit the extracellular Ca2+ uptake, preventing the premature acrosomal exocytosis and hyperactivation when sperm cells ascend through the female reproductive tract. The binding of caltrin proteins to specific areas of the sperm surface suggests the existence of caltrin receptors, or precise protein-phospholipid arrangements in the sperm membrane, distributed in the regions where Ca2+ influx may take place. However, the molecular mechanisms of recognition and interaction between caltrin and spermatozoa have not been elucidated. Therefore, the aim of this article is to describe in depth the known structural features and functional properties of caltrin proteins, to find out how they may possibly interact with the sperm membranes to control the intracellular signaling that trigger physiological events required for fertilization.

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