Current developments in antibiotic discovery

Hegemann, Julian D.; Birkelbach, Joy; Walesch, Sebastian; Müller, Rolf

doi:10.15252/embr.202256184

Cited by 30 publications

(27 citation statements)

References 18 publications

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“…In addition to isolating new bacteria from soil or marine samples, the investigation of animal and human microbiomes shows promise (Hegemann et al , 2022 ). The antibiotics lugdunin (Zipperer et al , 2016 ), lactocillin (Donia et al , 2014 ) and cutimycin (Claesen et al , 2020 ), isolated from human commensal bacteria, show activity against Gram‐positive bacteria.…”

Section: The Need For New Antibioticsmentioning

confidence: 99%

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

et al. 2022

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Antibacterial resistance is one of the greatest threats to human health. The development of new therapeutics against bacterial pathogens has slowed drastically since the approvals of the first antibiotics in the early and mid-20 th century. Most of the currently investigated drug leads are modifications of approved antibacterials, many of which are derived from natural products. In this review, we highlight the challenges, advancements and current standing of the clinical and preclinical antibacterial research pipeline. Additionally, we present novel strategies for rejuvenating the discovery process and advocate for renewed and enthusiastic investment in the antibacterial discovery pipeline.

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Section: The Need For New Antibioticsmentioning

confidence: 99%

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

et al. 2022

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“…NMR data for lagriamide B (2) have been deposited to the Natural Products Magnetic Resonance Database (https:// www.np-mrd.org) under accession code NP0332828. The structure of lagriamide B has been deposited to the Natural Products Atlas (https://www.npatlas.org).…”

Section: Data Availabilitymentioning

confidence: 99%

Discovery of a lagriamide polyketide by integrated genome mining, isotopic labeling, and untargeted metabolomics

Fergusson,

Saulog,

Paulo

et al. 2024

Chem. Sci.

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“…Most studies (56%) focused on actinomycetes (Figure 2C). While actinomycetes are indeed gifted (Gavriilidou et al 2022), mining of diverse phyla is expected to lead to further chemical diversity (Hegemann et al 2023).…”

Section: Bgc Prioritization Biosynthetic Class and Host Taxamentioning

confidence: 99%

Bacterial natural product discovery by heterologous expression

Kadjo,

Eustaquio

2023

Preprint

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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 realize bioinformatics predictions into products. However, challenges remain such as gene cluster prioritization, cloning of the complete gene cluster, appropriate expression, product identification, and isolation of products in practical yields. Here we reviewed the literature from the past five 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 identified. 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.

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Current developments in antibiotic discovery

Abstract: In light of the pending antibiotic resistance crisis, we need to go back to nature and search for novel anti‐bacterial compounds.

Cited by 30 publications

References 18 publications

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

Discovery of a lagriamide polyketide by integrated genome mining, isotopic labeling, and untargeted metabolomics

Bacterial natural product discovery by heterologous expression

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