Dark, rare and inspirational microbial matter in the extremobiosphere: 16 000 m of bioprospecting campaigns DOI
Alan T. Bull, Michael Goodfellow

Microbiology, Journal Year: 2019, Volume and Issue: 165(12), P. 1252 - 1264

Published: June 11, 2019

The rationale of our bioprospecting campaigns is that the extremobiosphere, particularly deep sea and hyper-arid deserts, harbours undiscovered biodiversity likely to express novel chemistry biocatalysts thereby providing opportunities for therapeutic drug industrial process development.We have focused on actinobacteria because their frequent role as keystone species in soil ecosystems unrivalled track record a source bioactive compounds.Population numbers diversity extremobiosphere are traditionally considered be low, although they often comprise dominant bacterial biota.Recent metagenomic evaluation 'the uncultured microbial majority' has now revealed enormous taxonomic among 'dark' 'rare' samples diverse sediments from depths Mariana Trench soils heights Central Andes.The application innovative culture screening options emphasize rigorous dereplication at each stage analysis, strain prioritization identify 'gifted' organisms, been deployed detect characterize hit compounds sought-after catalysts this hitherto untapped resource.The rewards include first-in-a-class chemical entities with modes action, well growing seed bank represents potentially biotechnological innovation.

Language: Английский

antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline DOI Creative Commons
Kai Blin, Simon J. Shaw, Kat Steinke

et al.

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: 47(W1), P. W81 - W87

Published: April 17, 2019

Abstract Secondary metabolites produced by bacteria and fungi are an important source of antimicrobials other bioactive compounds. In recent years, genome mining has seen broad applications in identifying characterizing new compounds as well metabolic engineering. Since 2011, the ‘antibiotics secondary metabolite analysis shell—antiSMASH’ (https://antismash.secondarymetabolites.org) assisted researchers this, both a web server standalone tool. It established itself most widely used tool for analysing biosynthetic gene clusters (BGCs) bacterial fungal sequences. Here, we present entirely redesigned extended version 5 antiSMASH. antiSMASH adds detection rules encoding biosynthesis acyl-amino acids, β-lactones, RiPPs, RaS-RiPPs, polybrominated diphenyl ethers, C-nucleosides, PPY-like ketones lipolanthines. For type II polyketide synthase-encoding clusters, now offers more detailed predictions. The HTML output visualization been to improve navigation visual representation annotations. We have again improved runtime steps, making it possible deliver comprehensive annotations genomes within few minutes. A file standard JavaScript object notation (JSON) format is aimed at downstream tools that process results programmatically.

Language: Английский

Citations

2737
antiSMASH 6.0: improving cluster detection and comparison capabilities DOI Creative Commons
Kai Blin, Simon J. Shaw, Alexander Kloosterman

et al.

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 49(W1), P. W29 - W35

Published: April 19, 2021

Abstract Many microorganisms produce natural products that form the basis of antimicrobials, antivirals, and other drugs. Genome mining is routinely used to complement screening-based workflows discover novel products. Since 2011, "antibiotics secondary metabolite analysis shell—antiSMASH" (https://antismash.secondarymetabolites.org/) has supported researchers in their microbial genome tasks, both as a free-to-use web server standalone tool under an OSI-approved open-source license. It currently most widely for detecting characterising biosynthetic gene clusters (BGCs) bacteria fungi. Here, we present updated version 6 antiSMASH. antiSMASH increases number cluster types from 58 71, displays modular structure multi-modular BGCs, adds new BGC comparison algorithm, allows integration results prediction tools, more effectively detects tailoring enzymes RiPP clusters.

Language: Английский

Citations

2132
Natural products targeting strategies involving molecular networking: different manners, one goal DOI
Alexander Ramos, Laurent Evanno, Erwan Poupon

et al.

Natural Product Reports, Journal Year: 2019, Volume and Issue: 36(7), P. 960 - 980

Published: Jan. 1, 2019

Covering: up to 2019Landmark advances in bioinformatics tools have recently enhanced the field of natural products research, putting today's product chemists enviable position being able perform efficient targeting/discovery previously undescribed molecules by expediting prioritization isolation workflow. Among these advances, MS/MS molecular networking has appeared as a promising approach dereplicate complex mixtures, leading real revolution "art isolation" accelerating pace research this field. This review illustrates through selected cornerstone studies new thinking drawing parallel between different underlying philosophies behind use targeting products.

Language: Английский

Citations

208
Extreme environments: microbiology leading to specialized metabolites DOI Open Access
Ahmed M. Sayed, Marwa H. A. Hassan, Hani A. Alhadrami

et al.

Journal of Applied Microbiology, Journal Year: 2019, Volume and Issue: 128(3), P. 630 - 657

Published: July 16, 2019

The prevalence of multidrug-resistant microbial pathogens due to the continued misuse and overuse antibiotics in agriculture medicine is raising prospect a return preantibiotic days at time diminishing numbers drug leads. good news that an increased understanding nature extent diversity natural habitats coupled with application new technologies microbiology chemistry opening up strategies search for specialized products therapeutic properties. This review explores premise harsh environmental conditions extreme biomes, notably deserts, permafrost soils deep-sea sediments select micro-organisms, especially actinobacteria, cyanobacteria fungi, potential synthesize druggable molecules. There evidence over past decade micro-organisms adapted life are rich source metabolites. Extreme by their very tend be fragile hence there need conserve those known hot-spots novel gifted needed drive discovery campaigns innovative biotechnology. also provides overview microbial-derived molecules biological activities focusing on period from 2010 until 2018, this 186 structures were isolated 129 representatives taxa recovered habitats.

Language: Английский

Citations

155
Strategies to access biosynthetic novelty in bacterial genomes for drug discovery DOI

Franziska Hemmerling,

Jörn Piel

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(5), P. 359 - 378

Published: March 16, 2022

Language: Английский

Citations

89
Microbiome composition modulates secondary metabolism in a multispecies bacterial community DOI Creative Commons
Marc G. Chevrette, Chris S. Thomas, Amanda Hurley

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(42)

Published: Oct. 10, 2022

Bacterial secondary metabolites are a major source of antibiotics and other bioactive compounds. In microbial communities, these molecules can mediate interspecies interactions responses to environmental change. Despite the importance in human health ecology, little is known about their roles regulation context multispecies communities. simplified model rhizosphere composed Bacillus cereus , Flavobacterium johnsoniae Pseudomonas koreensis we show that dynamics metabolism depend on community species composition interactions. Comparative metatranscriptomics metametabolomics reveal abundance transcripts biosynthetic gene clusters (BGCs) metabolomic molecular features differ between monocultures or dual cultures tripartite community. both two- three-member cocultures, P. modified expression BGCs for zwittermicin, petrobactin, B. F. johnsoniae, whereas BGC transcriptional response itself was minimal. Pairwise cocultures with displayed unique appear be derivatives lokisin, suggesting metabolic handoffs species. Deleting koreenceine, another metabolite, altered transcript metabolite profiles across community, including substantial up-regulation petrobactin bacillibactin koreenceine represses siderophore production. Results from this bacterial chemical output identity capacity coculture partners, microbiome may shape nature.

Language: Английский

Citations

76
The antiSMASH database version 4: additional genomes and BGCs, new sequence-based searches and more DOI Creative Commons
Kai Blin, Simon J. Shaw, Marnix H. Medema

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D586 - D589

Published: Oct. 30, 2023

Abstract Many microorganisms produce natural products that are frequently used in the development of medicines and crop protection agents. Genome mining has evolved into a prominent method to access this potential. antiSMASH is most popular tool for task. Here we present version 4 database, providing biosynthetic gene clusters detected by 7.1 publicly available, dereplicated, high-quality microbial genomes via an interactive graphical user interface. In 4, database contains 231 534 high quality BGC regions from 592 archaeal, 35 726 bacterial 236 fungal available at https://antismash-db.secondarymetabolites.org/.

Language: Английский

Citations

58
Microbial secondary metabolites: advancements to accelerate discovery towards application DOI
Jaime Lorenzo N. Dinglasan, Hiroshi Otani, Drew T. Doering

et al.

Nature Reviews Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

Citations

4
IMG-ABC v.5.0: an update to the IMG/Atlas of Biosynthetic Gene Clusters Knowledgebase DOI Creative Commons
Krishna Palaniappan, I-Min A. Chen, Ken Chu

et al.

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: unknown

Published: Oct. 10, 2019

Microbial secondary metabolism is a reservoir of bioactive compounds immense biotechnological and biomedical potential. The biosynthetic machinery responsible for the production these metabolites (SMs) (also called natural products) often encoded by collocated groups genes gene clusters (BGCs). High-throughput genome sequencing both isolates metagenomic samples combined with development specialized computational workflows enabling systematic identification BGCs discovery novel SMs. In order to advance exploration microbial its diversity, we developed largest publicly available database predicted experimentally verified BGCs, Integrated Genomes Atlas Biosynthetic Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc-public). Here describe first major content update IMG-ABC knowledgebase, since initial release in 2015, refreshing BGC prediction pipeline latest version antiSMASH (v5) as well presenting data context underlying environmental metadata sourced from GOLD (https://gold.jgi.doe.gov/). This has greatly improved quality expanded types compared previous version.

Language: Английский

Citations

97
Chemoenzymatic Total Synthesis of Natural Products DOI
Suman Chakrabarty, Evan O. Romero, Joshua B. Pyser

et al.

Accounts of Chemical Research, Journal Year: 2021, Volume and Issue: 54(6), P. 1374 - 1384

Published: Feb. 18, 2021

The total synthesis of structurally complex natural products has challenged and inspired generations chemists remains an exciting area active research. Despite their history as privileged bioactivity-rich scaffolds, the use in drug discovery waned. This shift is driven by relatively low abundance hindering isolation from sources challenges presented synthesis. Recent developments biocatalysis have resulted application enzymes for construction molecules. From inception Narayan lab 2015, we focused on harnessing exquisite selectivity alongside contemporary small molecule-based approaches to enable concise chemoenzymatic routes products.We various families that perform selective oxidation reactions. For example, targeted xyloketal through a strategy relies chemo- site-selective biocatalytic hydroxylation. Members family are characterized polycyclic ketal cores demonstrate potent neurological activity. We envisioned assembling representative product (xyloketal D) involving biocatalytically generated

Language: Английский

Citations

82