Identification of a solo acylhomoserine lactone synthase from the myxobacterium Archangium gephyra

AbstractConsidered a key taxon in soil and marine microbial communities, myxobacteria exist as coordinated swarms that utilize a combination of lytic enzymes and specialized metabolites to facilitate predation of microbes. This capacity to produce specialized metabolites and the associated abundance of biosynthetic pathways contained within their genomes have motivated continued drug discovery efforts from myxobacteria. Of all myxobacterial biosynthetic gene clusters deposited in the antiSMASH database, only one putative acylhomoserine lactone (AHL) synthase, agpI, was observed, in genome data from Archangium gephyra. Without an AHL receptor also apparent in the genome of A. gephyra, we sought to determine if AgpI was an uncommon example of an orphaned AHL synthase. Herein we report the bioinformatic assessment of AgpI and discovery of a second AHL synthase from Vitiosangium sp. During axenic cultivation conditions, no detectible AHL metabolites were observed in A. gephyra extracts. However, heterologous expression of each synthase in Escherichia coli provided detectible quantities of 3 AHL signals including 2 known AHLs, C8-AHL and C9-AHL. These results suggest that A. gephyra AHL production is dormant during axenic cultivation. The functional, orphaned AHL synthase, AgpI, is unique to A. gephyra, and its utility to the predatory myxobacterium remains unknown.

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Cryptic, solo acylhomoserine lactone synthase from predatory myxobacterium suggests beneficial contribution to prey quorum signaling

10.1101/849075 ◽

2019 ◽

Author(s):

Hanan Albataineh ◽

Maya Duke ◽

Sandeep K. Misra ◽

Joshua S. Sharp ◽

D. Cole Stevens

Keyword(s):

Microbial Communities ◽

Gene Clusters ◽

Biologically Active ◽

Interspecies Interactions ◽

Active Metabolites ◽

Lytic Enzymes ◽

Cultivation Conditions ◽

Acylhomoserine Lactone ◽

Polymicrobial Communities ◽

Axenic Cultivation

AbstractConsidered a key taxon in microbial communities, myxobacteria exist as coordinated swarms that utilize an excreted combination of lytic enzymes and specialized metabolites to facilitate predation of numerous microbial phyla. This capacity to produce biologically active metabolites and the associated abundance of natural product biosynthetic pathways contained within their genomes have motivated continued drug discovery efforts from myxobacteria. Of all the biosynthetic gene clusters associated with myxobacteria deposited in the antiSMASH database (∼1,000 total), only one putative acylhomoserine lactone synthase, agpI, was observed in genome data from the myxobacterium Archangium gephyra. Without an acylhomoserine lactone (AHL) receptor also apparent in the genome of A. gephyra, we sought to determine if AgpI was the first example of an orphaned AHL synthase. Herein we report the bioinformatic assessment of AgpI and discovery of a second myxobacterial AHL synthase from Vitiosangium sp. strain GDMCC 1.1324. During axenic cultivation conditions, no detectible AHL metabolites were observed in A. gephyra extracts. However, heterologous expression of each synthase in Escherichia coli provided detectible quantities of 3 AHL signals including 2 known AHLs, C8-AHL and C9-AHL. These results suggest that A. gephyra AHL production is dormant during axenic cultivation conditions and requires an unknown external cue for activation. The orphaned AHL synthase, AgpI, is the first to be reported from a predatory myxobacterium, and predator production of prey quorum signals provides unique insight into interspecies crosstalk within polymicrobial communities.ImportanceThe presence of orphaned quorum signal receptors and associated recognition and response to exogenous acylhomoserine lactone quorum signals observed in microbial communities provides evidence for small molecule-mediated interspecies interactions. While the high occurrence of orphaned AHL receptors from bacteria that do not produce cognate AHL signals suggests the involvement of AHL signals as a shared chemical resource in polymicrobial communities, no orphaned AHL synthases have been determined to be functional in a species without an associated AHL receptor. An orphan signal synthase from a predatory myxobacterium provides an alternative perspective on the evolution and benefits of quorum signaling systems within these communities.

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

10.1101/2020.06.24.170084 ◽

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.

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

10.1101/2020.12.19.423547 ◽

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

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Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

Nature Communications ◽

10.1038/s41467-021-25462-1 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 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.

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

10.1101/631242 ◽

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.

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luxRHomolog-Linked Biosynthetic Gene Clusters inProteobacteria

mSystems ◽

10.1128/msystems.00208-17 ◽

2018 ◽

Vol 3 (3) ◽

Cited By ~ 11

Author(s):

Carolyn A. Brotherton ◽

Marnix H. Medema ◽

E. Peter Greenberg

Keyword(s):

Genome Mining ◽

Gene Clusters ◽

Growth Conditions ◽

Bioactive Metabolites ◽

Growth Media ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Specialized Metabolites ◽

A Genome ◽

Functionally Diverse

ABSTRACTMicrobes are a major source of antibiotics, pharmaceuticals, and other bioactive compounds. The production of many specialized microbial metabolites is encoded in biosynthetic gene clusters (BGCs). A challenge associated with natural product discovery is that many BGCs are not expressed under laboratory growth conditions. Here we report a genome-mining approach to discover BGCs withluxR-type quorum sensing (QS) genes, which code for regulatory proteins that control gene expression. Our results show that BGCs linked to genes coding for LuxR-like proteins are widespread inProteobacteria. In addition, we show that associations betweenluxRhomolog genes and BGCs have evolved independently many times, with functionally diverse gene clusters. Overall, these clusters may provide a source of new natural products for which there is some understanding about how to elicit production.IMPORTANCEBacteria biosynthesize specialized metabolites with a variety of ecological functions, including defense against other microbes. Genes that code for specialized metabolite biosynthetic enzymes are frequently clustered together. These BGCs are often regulated by a transcription factor encoded within the cluster itself. These pathway-specific regulators respond to a signal or indirectly through other means of environmental sensing. Many specialized metabolites are not produced under laboratory growth conditions, and one reason for this issue is that laboratory growth media lack environmental cues necessary for BGC expression. Here, we report a bioinformatics study that reveals that BGCs are frequently linked to genes coding for LuxR family QS-responsive transcription factors in the phylumProteobacteria. The products of theseluxRhomolog-associated gene clusters may serve as a practical source of bioactive metabolites.

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Phages weaponize their bacteria with biosynthetic gene clusters

10.1101/2020.10.01.322628 ◽

2020 ◽

Author(s):

Anna Dragoš ◽

Aaron J.C. Andersen ◽

Carlos N. Lozano-Andrade ◽

Paul J. Kempen ◽

Ákos T. Kovács ◽

...

Keyword(s):

Pathogenic Bacteria ◽

Gene Clusters ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Specialized Metabolites ◽

Fitness Advantage ◽

Large Step ◽

Bioactive Potential ◽

Close Relatives

ABSTRACTBacteria produce many different specialized metabolites, which are encoded by biosynthetic gene clusters (BGCs). Despite high industrial relevance owing to broad bioactive potential of these metabolites, their ecological roles remain largely unexplored. We analyze all available genomes for BGCs of phage origin. The BGCs predominantly reside within temperate phages infecting certain commensal and pathogenic bacteria. Nearly all phage BGCs encode bacteriocins, which appear to serve as a strong proxy for phage specificity. Using the gut-associated bacterium Bacillus subtilis, we demonstrate how a temperate phage equips its host with a functional BGC, providing it with a competitive fitness advantage over close relatives. Therefore, certain temperate phages use BGCs to weaponize their bacteria against close relatives, leading to evolutionary benefits from lysogeny to the infected host, and hence, to the phage itself. Our study is a large step towards understanding the natural role of specialized metabolites, as well as mutualistic phage-host relationships.

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Production of Plant-Associated Volatiles by Select Model and Industrially Important Streptomyces spp.

Microorganisms ◽

10.3390/microorganisms8111767 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1767 ◽

Cited By ~ 1

Author(s):

Zhenlong Cheng ◽

Sean McCann ◽

Nicoletta Faraone ◽

Jody-Ann Clarke ◽

E. Abbie Hudson ◽

...

Keyword(s):

Mass Spectrometry ◽

Gas Chromatography ◽

Biological Activities ◽

Gene Clusters ◽

Gas Chromatography Mass Spectrometry ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Specialized Metabolites ◽

Streptomyces Spp ◽

Volatile Organic

The Streptomyces produce a great diversity of specialized metabolites, including highly volatile compounds with potential biological activities. Volatile organic compounds (VOCs) produced by nine Streptomyces spp., some of which are of industrial importance, were collected and identified using gas chromatography–mass spectrometry (GC-MS). Biosynthetic gene clusters (BGCs) present in the genomes of the respective Streptomyces spp. were also predicted to match them with the VOCs detected. Overall, 33 specific VOCs were identified, of which the production of 16 has not been previously reported in the Streptomyces. Among chemical classes, the most abundant VOCs were terpenes, which is consistent with predicted biosynthetic capabilities. In addition, 27 of the identified VOCs were plant-associated, demonstrating that some Streptomyces spp. can also produce such molecules. It is possible that some of the VOCs detected in the current study have roles in the interaction of Streptomyces with plants and other higher organisms, which might provide opportunities for their application in agriculture or industry.

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Draft Genome Sequence of Bacillus sp. Strain M21, Isolated from the Arid Area of Matmata, Tunisia

Genome Announcements ◽

10.1128/genomea.00323-18 ◽

2018 ◽

Vol 6 (17) ◽

Cited By ~ 1

Author(s):

Zina Nasfi ◽

Anja Poehlein ◽

Henrik Harms ◽

Emilie Goralski ◽

Katja M. Fisch ◽

...

Keyword(s):

Draft Genome ◽

Gene Clusters ◽

Arid Area ◽

Bacillus Sp ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Total Size ◽

Gram Negative ◽

Content Type ◽

Specialized Metabolites

ABSTRACT Bacillus sp. strain M21 was isolated from an environmental sample. In antibacterial screenings, the strain inhibited growth of Gram-positive and Gram-negative test strains. The genome was assembled into 69 contigs with a total size of 5.178 Mb. The strain contains at least nine biosynthetic gene clusters for the production of specialized metabolites.

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Vertical Inheritance Facilitates Interspecies Diversification in Biosynthetic Gene Clusters and Specialized Metabolites

mBio ◽

10.1128/mbio.02700-21 ◽

2021 ◽

Author(s):

Alexander B. Chase ◽

Douglas Sweeney ◽

Mitchell N. Muskat ◽

Dulce G. Guillén-Matus ◽

Paul R. Jensen

Keyword(s):

Natural Products ◽

Gene Clusters ◽

Species Level ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Evolutionary Processes ◽

Vertical Inheritance ◽

Metabolite Production ◽

Specialized Metabolites ◽

Microbial Natural Products

Microbial natural products are traditionally exploited for their pharmaceutical potential, yet our understanding of the evolutionary processes driving BGC evolution and compound diversification remains poorly developed. While HGT is recognized as an integral driver of BGC distributions, we find that the effects of vertical inheritance on BGC diversification had direct implications for species-level specialized metabolite production.

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