Mining prokaryotes for antimicrobial compounds: from diversity to function

Tracanna, Vittorio; Jong, Anne de; Medema, Marnix H.; Kuipers, Oscar P.

doi:10.1093/femsre/fux014

Cited by 93 publications

(105 citation statements)

References 88 publications

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“…Genome-mining studies based on these enzymes have revealed that lanthipeptide BGCs are distributed widely across bacterial phyla [19][20][21][22][23][24][25][26][27][28][29]. Despite the success in bioinformatically identifying likely lanthipeptide BGCs, it has been an outstanding challenge to perform high-throughput analysis of the precursor peptides encoded in these gene clusters.…”

mentioning

confidence: 99%

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Walker

Mitchell

Donk

2020

Preprint

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BackgroundLanthipeptides belong to the ribosomally synthesized and post-translationally modified peptide group of natural products and have a variety of biological activities ranging from antibiotics to antinociceptives. These peptides are cyclized through thioether crosslinks and can bear other secondary post-translational modifications. While lanthipeptide biosynthetic gene clusters can be identified by the presence of characteristic enzymes involved in the post-translational modification of these peptides, locating the precursor peptides encoded within these clusters is challenging due to their short length and high sequence variability, which limits the high-throughput exploration of lanthipeptide precursor peptides. To address this challenge, we enhanced the predictive capabilities of Rapid ORF Description & Evaluation Online (RODEO) to identify all known classes of lanthipeptides. ResultsUsing RODEO, we mined over 100,000 bacterial and archaeal genomes in the RefSeq database. We identified nearly 8,500 lanthipeptide precursor peptides. These precursor peptides were identified in a broad range of bacterial phyla as well as the Euryarchaeota phylum of archaea. Bacteroidetes were found to encode a large number of these biosynthetic gene clusters, despite making up a relatively small portion of the genomes in this dataset. While a number of these precursor peptides are similar to those of previously characterized lanthipeptides, even more were not, including potential antibiotics. Additionally, examination of the biosynthetic gene clusters revealed enzymes that install secondary post-translational modifications are more widespread than initially thought. ConclusionLanthipeptide biosynthetic gene clusters are more widely distributed and the precursor peptides encoded within these clusters are more diverse than previously appreciated, demonstrating that the lanthipeptide sequence-function space remains largely underexplored.

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confidence: 99%

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Walker

Mitchell

Donk

2020

Preprint

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“…20% of all analyzed bacteria synthesize only one RiPP cluster, but up to 11 RiPPs produced by one single organism could also be identified (Skinnider et al ., ). Various ways of screening for antimicrobials were recently reviewed (Tracanna et al ., ). These gene clusters comprise, besides structural genes, genes encoding modification enzymes and transporters, which have to be tightly regulated to guarantee a fully modified active peptide.…”

Section: Discussionmentioning

confidence: 97%

Major gene‐regulatory mechanisms operating in ribosomally synthesized and post‐translationally modified peptide (RiPP) biosynthesis

Bartholomae

Buivydas

Viel

et al. 2017

Molecular Microbiology

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Summary Post‐translationally modified peptides commonly display antimicrobial activity, but can also aid the development of bacterial colonies, giving a competitive advantage in the ecological niche. The production of post‐translationally modified peptides by bacteria is a complex and energetically costly process that is strictly orchestrated in the cell. The onset of peptide production is linked to the different enzymes that take part during maturation, the transporters and the immunity determinants (if required). Thus, the population can make optimal use of available resources and obtain the benefits of production at an advantageous moment during growth, avoiding toxicity to itself. The timing and level of expression of the different operons is controlled by diverse (complex) regulatory pathways in response to environmental changes, stress or master regulators during specific growth transition phases. In this review, we highlight the basic principles and mechanisms of regulation of expression of post‐translationally modified peptides and the relationship with the overall culture developmental processes and/or cellular differentiation. We also discuss the biotechnological consequences derived from the understanding of regulatory networks involved in the biosynthesis of these natural products.

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“…178,179 The LPs produced by members of the Pseudomonas and Bacillus genera are structurally and functionally highly diverse, 165 further corroborated by the extensive genomic variability at the relevant BGCs. 171,180 3. In silico and in vivo mining for functional biosynthetic pathways of novel small natural compounds 3.1.…”

Section: Stimulatory Compoundsmentioning

confidence: 99%

Microbial small molecules – weapons of plant subversion

et al. 2018

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Covering: up to 2018 Plants live in close association with a myriad of microbes that are generally harmless. However, the minority of microbes that are pathogens can severely impact crop quality and yield, thereby endangering food security. By contrast, beneficial microbes provide plants with important services, such as enhanced nutrient uptake and protection against pests and diseases. Like pathogens, beneficial microbes can modulate host immunity to efficiently colonize the nutrient-rich niches within and around the roots and aerial tissues of a plant, a phenomenon mirroring the establishment of commensal microbes in the human gut. Numerous ingenious mechanisms have been described by which pathogenic and beneficial microbes in the plant microbiome communicate with their host, including the delivery of immune-suppressive effector proteins and the production of phytohormones, toxins and other bioactive molecules. Plants signal to their associated microbes via exudation of photosynthetically fixed carbon sources, quorum-sensing mimicry molecules and selective secondary metabolites such as strigolactones and flavonoids. Molecular communication thus forms an integral part of the establishment of both beneficial and pathogenic plant-microbe relations. Here, we review the current knowledge on microbe-derived small molecules that can act as signalling compounds to stimulate plant growth and health by beneficial microbes on the one hand, but also as weapons for plant invasion by pathogens on the other. As an exemplary case, we used comparative genomics to assess the small molecule biosynthetic capabilities of the Pseudomonas genus; a genus rich in both plant pathogenic and beneficial microbes. We highlight the biosynthetic potential of individual microbial genomes and the population at large, providing evidence for the hypothesis that the distinction between detrimental and beneficial microbes is increasingly fading. Knowledge on the biosynthesis and molecular activity of microbial small molecules will aid in the development of successful biological agents boosting crop resiliency in a sustainable manner and could also provide scientific routes to pathogen inhibition or eradication.

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Mining prokaryotes for antimicrobial compounds: from diversity to function

Cited by 93 publications

References 88 publications

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Major gene‐regulatory mechanisms operating in ribosomally synthesized and post‐translationally modified peptide (RiPP) biosynthesis

Microbial small molecules – weapons of plant subversion

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