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{"Abstract":["Some bacteria use acyl-homoserine lactone (AHL) signals in quorum sensing,\n a type of cell-cell communication. Here we present “RefAHL”, a curated\n collection of LuxI-type AHL synthases with their AHL structures and\n associated metadata. RefAHL is publicly available as a community resource\n to help catalog LuxI-type diversity encoded in (meta)genomic data."],"Methods":["The RefAHL dataset was collected, assembled and curated by humans\n from the public scientific literature."],"TechnicalInfo":["# RefAHL: A curated quorum sensing reference linking diverse LuxI-type\n signal synthases with their acyl-homoserine lactone products Dataset DOI:\n [10.5061/dryad.866t1g21s](10.5061/dryad.866t1g21s) ## Description of the\n data and file structure Here we curate a list of previously published LuxI\n homologs, which have been experimentally demonstrated to synthesize an\n acyl homoserine lactone (AHL) signal of well-supported structure. We refer\n to this collection as “RefAHL” and will update the collection when new\n LuxI-AHL signals are defined. Contact Amy Schaefer\n ([amyschae@uw.edu](mailto:amyschae@uw.edu)) or Aaron Puri\n ([a.puri@utah.edu](mailto:a.puri@utah.edu)) with any questions or to\n submit newly defined LuxI-AHL signal pairs. There are two associated files\n (note that date suffixes in YYYYMMDD format will change in future\n versions). ### Files and variables #### File:\n RefAHL\\_complete\\_revYYYYMMDD.xlsx **Description:** The\n RefAHL_complete_revYYYYMMDD.xlsx file has Tab 1 ("RefAHL\n LuxI-AHL"), Tab 2 (“AHL compounds”), and Tab 3 ("RefAHL\n confidence ranking"), which contain the following variables (columns)\n and their descriptions: ##### Variables * (1) RefAHL identifier: Unique\n RefAHL name, comprised from the beginning of the genera/clone name\n (letters) and a number; if a LuxI homolog has >65% amino acid identity\n and synthesizes the same AHL product with an existing RefAHL LuxI, they\n are given the same RefAHL ID with a subcategory letter (e.g. Mes_001a,\n Mes_001b) (1) Taxonomy or clone: Indicates either bacterial Class taxonomy\n or clone if derived from metagenomic sequence (1) Published LuxI homolog\n name: Most, but not all, LuxI homologs have an associated gene/protein\n name; for those homologs in the same RefAHL identifier grouping the shared\n percent amino acid identity is indicated in parentheses (1) Major AHL\n (defined in Tab 2): The abbreviation of the major AHL signal synthesized\n by the LuxI homolog; in cases where cognate LuxR activity data is not\n available, the major AHL is defined as the most abundant AHL produced; see\n Tab 2 for full compound names and additional chemical information; in\n cases where the major AHL depends on the growth condition or strain\n background, this is listed in parentheses [e.g. in minimal medium (M9) vs.\n rich medium (K9) for Burk_007] (1) AHL confidence category (defined in Tab\n 3): Confidence category ranking for the AHL product synthesized by the\n LuxI homolog depending upon its associated data; see Tab 3 for specific\n criteria (1) Strain or metagenome: Name of the bacterial strain or\n metagenomic library clone encoding the LuxI homolog gene (1) Reference(s)\n (PMID): Reference(s) for the data summarized in RefAHL; in most cases this\n is the PubMed identifier (PMID) number for published manuscript(s); one\n entry references unpublished 14C-methionine feeding data, which supports\n the published relaxed-specificity bioassay data (1) LuxI-homolog protein\n sequence: Amino acid sequence of the LuxI homolog (1) IMG gene\n identifier: Unique object identifier of the LuxI homolog gene in the\n JGI-IMG database; ‘none’ indicates the genome sequence is not hosted by\n IMG (1) GenBank identifier: Unique object identifier of the LuxI homolog\n gene in the GenBank database; only used when there was no IMG identifier\n available * (2) AHL abbreviation: Abbreviation of the acyl homoserine\n lactone (AHL) structure used in Tab 1 (2) AHL common name: Common chemical\n name of the AHL structure (2) PubChem compound: Unique object identifier\n of the AHL structure in the NIH PubChem database; ‘not available’\n indicates the AHL has an undefined double bond so a PubChem number cannot\n be assigned; 'none' indicates the compound has not been\n deposited in PubChem (2) AHL isomeric SMILES: The isomeric Simplified\n Molecular Input Line Entry System sstructure line notation, which\n describes the AHL structures; we assume a stereochemistry of L for the\n homoserine lactone and R for any 3-hydroxy acyl groups; ‘not available’\n indicates the AHL has an undefined double bond so an isomeric SMILES\n cannot be assigned (2) AHL formula: Chemical formula for the AHL structure\n (2) AHL monoisotopic mass: Monoisotopic mass for the AHL structure * (3)\n Category: Confidence ranking of data used to assign the AHL structure;\n lower values denote better confidence (3) Criteria: Criteria used to\n assign the category confidence rank; the rationale for omitting data\n (superscript note a) that utilize only relaxed-specificity bioassays is\n discussed in the manuscript text #### File: RefAHL\\_rev20250421.fasta\n **Description:** The RefAHL_revYYYYMMDD.fasta file contains the following:\n Header: Contains the RefAHL identifier and Major AHL separated by an\n underscore for each LuxI homolog entry listed in .xls spreadsheet in fasta\n format; the text ‘RefAHL’ is included for each header for easy filtering\n Sequence: One letter coded amino acid sequence for the LuxI homolog ##\n Code/software .xlsx files can be opened with any version of Microsoft\n Excel, as well as Google Sheets, WPS Office or OpenOffice Calc .fasta\n files can be opened with any text editor ## Access information Other\n publicly accessible locations of the data: * none Data was derived from\n the following sources: * data was assembled from the original references\n as cited in RefAHL."]}
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Synergistic activity of cosecreted natural products from amoebae-associated bacteria
Investigating microbial interactions from an ecological perspective is a particularly fruitful approach to unveil both new chemistry and bioactivity. Microbial predator–prey interactions in particular rely on natural products as signal or defense molecules. In this context, we identified a grazing-resistant Pseudomonas strain, isolated from the bacterivorous amoeba Dictyostelium discoideum. Genome analysis of this bacterium revealed the presence of two biosynthetic gene clusters that were found adjacent to each other on a contiguous stretch of the bacterial genome. Although one cluster codes for the polyketide synthase producing the known antibiotic mupirocin, the other cluster encodes a nonribosomal peptide synthetase leading to the unreported cyclic lipopeptide jessenipeptin. We describe its complete structure elucidation, as well as its synergistic activity against methicillin-resistant Staphylococcus aureus , when in combination with mupirocin. Both biosynthetic gene clusters are regulated by quorum-sensing systems, with 3-oxo-decanoyl homoserine lactone (3-oxo-C10-AHL) and hexanoyl homoserine lactone (C6-AHL) being the respective signal molecules. This study highlights the regulation, richness, and complex interplay of bacterial natural products that emerge in the context of microbial competition.
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- PAR ID:
- 10098332
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 115
- Issue:
- 15
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- 3758 to 3763
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Newton, Irene_L G (Ed.)ABSTRACT Some bacteria use acyl-homoserine lactone (AHL) signals in quorum sensing, a type of cell-cell communication. Here, we present “RefAHL,” an updated, curated collection of LuxI-type AHL synthases with their AHL products and associated metadata. RefAHL is publicly available as a community resource to help catalog LuxI-type diversity encoded in (meta) genomic data.more » « less
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Abstract Natural products have found important applications in the pharmaceutical and agricultural sectors. In bacteria, the genes that encode the biosynthesis of natural products are often colocalized in the genome, forming biosynthetic gene clusters. It has been predicted that only 3% of natural products encoded in bacterial genomes have been discovered thus far, in part because gene clusters may be poorly expressed under laboratory conditions. Heterologous expression can help convert bioinformatics predictions into products. However, challenges remain, such as gene cluster prioritization, cloning of the complete gene cluster, high level expression, product identification, and isolation of products in practical yields. Here we reviewed the literature from the past 5 years (January 2018 to June 2023) to identify studies that discovered natural products by heterologous expression. From the 50 studies identified, we present analyses of the rationale for gene cluster prioritization, cloning methods, biosynthetic class, source taxa, and host choice. Combined, the 50 studies led to the discovery of 63 new families of natural products, supporting heterologous expression as a promising way to access novel chemistry. However, the success rate of natural product detection varied from 11% to 32% based on four large-scale studies that were part of the reviewed literature. The low success rate makes it apparent that much remains to be improved. The potential reasons for failure and points to be considered to improve the chances of success are discussed. One-Sentence SummaryAt least 63 new families of bacterial natural products were discovered using heterologous expression in the last 5 years, supporting heterologous expression as a promising way to access novel chemistry; however, the success rate is low (11–32%) making it apparent that much remains to be improved—we discuss the potential reasons for failure and points to be considered to improve the chances of success. BioRender was used to generate the graphical abstract figure.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1073/pnas.1721790115
