Targeted Dereplication of Microbial Natural Products by High-Resolution MS and Predicted LC Retention Time

Chervin, J; Stierhof, Marc; Tong, Ming Him; Peace, Doe; Hansen, Kine Østnes; Urgast, Dagmar S.; Andersen, Jeanette Hammer; Yu, Yi; Ebel, Rainer; Kyeremeh, Kwaku; Paget, V; Cîmpan, Gabriela; Wyk, Albert van; Deng, Hai; Jaspars, Marcel; Tabudravu, Jioji N.

doi:10.1021/acs.jnatprod.6b01035

Cited by 27 publications

(17 citation statements)

References 36 publications

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“…Established approaches such as bioassay-guided screening coupled with compound purification and structure determination, and metabolomics (chemical fingerprinting of an organism, i.e. the product of genotype and environment), have been complemented by genome-based techniques such as mining of whole and metagenomes, and crucially by database developments designed to promote chemical dereplication [13].…”

Section: The Paradigm Shiftmentioning

confidence: 99%

Dark, rare and inspirational microbial matter in the extremobiosphere: 16 000 m of bioprospecting campaigns

Bull

Goodfellow

2019

Microbiology

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

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Section: The Paradigm Shiftmentioning

confidence: 99%

Dark, rare and inspirational microbial matter in the extremobiosphere: 16 000 m of bioprospecting campaigns

Bull

Goodfellow

2019

Microbiology

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“…This concept has been successfully utilised to characterise, identify, and discriminate samples. 15,27,33 In this context, the data processing algorithm, ACD/IntelliXtract (IX), part of the ACD/MS Workbook Suite 34 was scripted to provide metrics on sample novelty (number of unidentified m/z ions over the total number of detectable ions), chemical novelty (total number of identified masses in the sample over the total number of ions), sample complexity (number of peaks above a defined threshold), and sample diversity (abundance) taking into consideration peak areas and heights.…”

Section: Resultsmentioning

confidence: 99%

“…26 Recently, we proposed a new strategy of identifying known microbial natural products utilising a combination of HRMS and predicted LC retention time of 5,098 compounds from Streptomyces. 27 Another approach used a predicted 13 C NMR chemical shifts database to screen for similar compounds in an extract. 28 The goal of this study was to develop a LC-HRMS-database-software-integrated tool that can process, screen, and prioritise samples based on three metrics: novelty, complexity and diversity.…”

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confidence: 99%

LC-HRMS-Database Screening Metrics for Rapid Prioritization of Samples to Accelerate the Discovery of Structurally New Natural Products

et al. 2019

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In order to accelerate the isolation and characterisation of structurally new or novel secondary metabolites, it is crucial to develop efficient strategies that prioritise samples with greatest promise early in the workflow so that resources can be utilised in a more efficient and costeffective manner. We have developed a metrics-based prioritisation approach using exact LC-HRMS which uses data for 24,618 marine natural products held in the PharmaSea database. Each sample was evaluated and allocated a metric score by a software algorithm based on the ratio of new masses over the total (sample novelty), ratio of known masses over the total (chemical novelty), number of peaks above a defined peak area threshold (sample complexity), and peak area (sample diversity). Samples were then ranked and prioritized based on these metric scores. To validate the approach, 8 marine sponges and 6 tunicate samples collected from the Fiji Islands were analysed, metric scores calculated and samples targeted for isolation and characterisation of new compounds. Structures of new compounds were elucidated by spectroscopic techniques, including 1D and 2D NMR, MS and MS/MS. Structures were confirmed by Computer Assisted Structure Elucidation methods (CASE) using the ACD/Structure Elucidator Suite.

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“…Nowadays, it is much more challenging than before to discover new antibiotics by simply using actinobacteria-based screening [11,12]. Thus, many new strategies and innovative approaches are involved to break through the issue, such as exploitation of new antibiotics from unique and underexplored habits, novel culturing approaches to isolate novel species thought to be uncultivable, new screening models, activation of cryptic biosynthetic pathway, genomes mining [7,[13][14][15][16][17][18], and using modern analytic techniques coupled with powerful databases [19][20][21][22][23][24][25], since it is believed that actinobacteria is still a source of novel antibiotics [26,27].…”

Section: Introductionmentioning

confidence: 99%

Exploitation of Potentially New Antibiotics from Mangrove Actinobacteria in Maowei Sea by Combination of Multiple Discovery Strategies

Huang

et al. 2019

Antibiotics

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Rediscovery of known antibiotics from actinobacteria, especially Streptomyces, has become a bottleneck issue. Nowadays, more specific identification and dereplication could be acquired by a combination of modern analytic techniques with various databases. In this study, 261 actinobacterial strains were isolated from 8 mangrove soil samples by culture-dependent method. A total of 83 strains were selected to evaluate antibacterial activities and mechanisms by disc diffusion method and a unique double fluorescent protein reporter system (pDualrep2), respectively. Thirty-two strains exhibited antagonistic activity against at least one of the “ESKAPE” pathogens. Four Streptomyces strains (B475, B486, B353, and B98) showed strong inhibitory activity against Gram-positive bacteria and induced DNA damage SOS response. One Micromonospora strain (B704) exhibited inhibitory activity against several pathogens and induced attenuation-based translational inhibitors reporter. Seven members of quinoxaline-type antibiotics including quinomycin A, quinomycin monosulfoxide, and other five putative new analogues were found from the culture broth of strain B475 by a combination of anti-MRSA guide, HPTLC, HPLC-UV, and UPLC-UV-HRESIMS/MS analysis, Chemspider searching, and MS/MS-based molecular networking analysis. In conclusion, this study not only demonstrated that mangrove is a rich source of actinobacteria with the potentially new antibiotics but showed rapid dereplication of known antibiotics in the early stage can improve efficiency for the discovery of new antibiotics.

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Targeted Dereplication of Microbial Natural Products by High-Resolution MS and Predicted LC Retention Time

Cited by 27 publications

References 36 publications

Dark, rare and inspirational microbial matter in the extremobiosphere: 16 000 m of bioprospecting campaigns

Dark, rare and inspirational microbial matter in the extremobiosphere: 16 000 m of bioprospecting campaigns

LC-HRMS-Database Screening Metrics for Rapid Prioritization of Samples to Accelerate the Discovery of Structurally New Natural Products

Exploitation of Potentially New Antibiotics from Mangrove Actinobacteria in Maowei Sea by Combination of Multiple Discovery Strategies

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