Strategies to access biosynthetic novelty in bacterial genomes for drug discovery

Hemmerling, Franziska; Piel, Jörn

doi:10.1038/s41573-022-00414-6

Cited by 75 publications

(64 citation statements)

References 236 publications

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“…Microorganisms produce diverse secondary metabolites that mediate competition, communication, and other interactions with surrounding organisms ( 1 – 4 ). Such molecules have various biological activities, some of which facilitate symbiosis between microorganisms and animal hosts ( 5 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

Diaphorin, a Polyketide Produced by a Bacterial Symbiont of the Asian Citrus Psyllid, Inhibits the Growth and Cell Division of Bacillus subtilis but Promotes the Growth and Metabolic Activity of Escherichia coli

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Diaphorin, a Polyketide Produced by a Bacterial Symbiont of the Asian Citrus Psyllid, Inhibits the Growth and Cell Division of Bacillus subtilis but Promotes the Growth and Metabolic Activity of Escherichia coli

et al. 2022

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“…Microorganisms produce diverse secondary metabolites that mediate competition, communication, and other interactions with surrounding organisms and the environment (1)(2)(3)(4). Such molecules have various biological activities, some of which facilitate symbiosis between microorganisms and animal hosts (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Diaphorin, a polyketide produced by a bacterial symbiont of the Asian citrus psyllid, inhibits the growth of Bacillus subtilis but promotes the growth of Escherichia coli

Tanabe

Takasu

Hirose

et al. 2022

Preprint

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Diaphorin is a polyketide produced by Candidatus Profftella armatura (Gammaproteobacteria: Burkholderiales), an obligate symbiont of a notorious agricultural pest, the Asian citrus psyllid Diaphorina citri (Hemiptera: Psyllidae). Diaphorin belongs to the pederin family of bioactive agents found in various host-symbiont systems, including beetles, lichens, and sponges, harboring phylogenetically diverse bacterial producers. Previous studies showed that diaphorin has inhibitory effects on various eukaryotes, including the natural enemies of D. citri. However, little is known about its effects on prokaryotic organisms. To address this issue, the present study assessed the biological activities of diaphorin on two model prokaryotes, Escherichia coli (Gammaproteobacteria: Enterobacterales) and Bacillus subtilis (Firmicutes: Bacilli). The analyses revealed that diaphorin inhibits the growth of B. subtilis but moderately promotes the growth of E. coli. This finding implies that diaphorin functions as a defensive agent of the holobiont (host + symbionts) against some bacterial lineages but is beneficial for others, which potentially include obligate symbionts of D. citri.ImportanceCertain secondary metabolites, including antibiotics, evolve to mediate interactions among organisms. These molecules have distinct spectra for microorganisms and are often more effective against Gram-positive bacteria than Gram-negative ones. However, it is rare that a single molecule has completely opposite activities on distinct bacterial lineages. The present study revealed that a secondary metabolite synthesized by an organelle-like bacterial symbiont of psyllids inhibits the growth of Gram-positive Bacillus subtilis but promotes the growth of Gram-negative Escherichia coli. This finding not only provides insights into the evolution of symbiosis between animal hosts and bacteria but may also potentially be exploited to promote the effectiveness of industrial material production by microorganisms.

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“…When the recombinant SurE was mixed with 16, the linear precursor 16 was efficiently transformed into 2 without any detectable by-products. These results strongly indicated that SurE plays a role in both chain termination and macrocyclization in the biosynthesis of surugamides A-E (1)(2)(3)(4)(5).…”

Section: Total Synthesis Of Surugamide B and Identification Of A New ...mentioning

confidence: 67%

Total syntheses of surugamides and thioamycolamides toward understanding their biosynthesis

Kuranaga

2022

J Nat Med

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Peptidic natural products have received much attention as potential drug leads, and biosynthetic studies of peptidic natural products have contributed to the field of natural product chemistry over the past several decades. However, the key biosynthetic intermediates are generally not isolated from natural sources, and this can hamper a detailed analysis of biosynthesis. Furthermore, reported unusual structures, which are targets for biosynthetic studies, are sometimes the results of structural misassignments. Chemical synthesis techniques are imperative in solving these problems. This review focuses on the chemical syntheses of surugamides and thioamycolamides toward understanding their biosynthesis. These studies can provide the key biosynthetic intermediates that can reveal the biosynthetic pathways and/or true structures of these natural products. Graphical abstract

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Strategies to access biosynthetic novelty in bacterial genomes for drug discovery

Cited by 75 publications

References 236 publications

Diaphorin, a Polyketide Produced by a Bacterial Symbiont of the Asian Citrus Psyllid, Inhibits the Growth and Cell Division of Bacillus subtilis but Promotes the Growth and Metabolic Activity of Escherichia coli

Diaphorin, a Polyketide Produced by a Bacterial Symbiont of the Asian Citrus Psyllid, Inhibits the Growth and Cell Division of Bacillus subtilis but Promotes the Growth and Metabolic Activity of Escherichia coli

Diaphorin, a polyketide produced by a bacterial symbiont of the Asian citrus psyllid, inhibits the growth of Bacillus subtilis but promotes the growth of Escherichia coli

Total syntheses of surugamides and thioamycolamides toward understanding their biosynthesis

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