Corynecin (chloramphenicol analogs) fermentation studies: Selective production of Corynecin I by <i>Corynebacterium hydrocarboclastus</i> grown on acetate

Nakano, Hirofumi; Tomita, Fusao; Yamaguchi, Ken; Nagashima, Minoru; Suzuki, Takeo

doi:10.1002/bit.260190705

Cited by 12 publications

(3 citation statements)

References 15 publications

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“…Corynecins are a family of N -acyl derivatives of d -threo- p -nitrophenylserinol compounds, structurally related to the antibiotic chloramphenicol [ 111 ]. Since NRPS #5 of Rhodococcus sp.…”

Section: Resultsmentioning

confidence: 99%

Rhodococcus comparative genomics reveals a phylogenomic-dependent non-ribosomal peptide synthetase distribution: insights into biosynthetic gene cluster connection to an orphan metabolite

et al. 2021

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Natural products (NPs) are synthesized by biosynthetic gene clusters (BGCs), whose genes are involved in producing one or a family of chemically related metabolites. Advances in comparative genomics have been favourable for exploiting huge amounts of data and discovering previously unknown BGCs. Nonetheless, studying distribution patterns of novel BGCs and elucidating the biosynthesis of orphan metabolites remains a challenge. To fill this knowledge gap, our study developed a pipeline for high-quality comparative genomics for the actinomycete genus Rhodococcus , which is metabolically versatile, yet understudied in terms of NPs, leading to a total of 110 genomes, 1891 BGCs and 717 non-ribosomal peptide synthetases (NRPSs). Phylogenomic inferences showed four major clades retrieved from strains of several ecological habitats. BiG-SCAPE sequence similarity BGC networking revealed 44 unidentified gene cluster families (GCFs) for NRPS, which presented a phylogenomic-dependent evolution pattern, supporting the hypothesis of vertical gene transfer. As a proof of concept, we analysed in-depth one of our marine strains, Rhodococcus sp. H-CA8f, which revealed a unique BGC distribution within its phylogenomic clade, involved in producing a chloramphenicol-related compound. While this BGC is part of the most abundant and widely distributed NRPS GCF, corason analysis unveiled major differences regarding its genetic context, co-occurrence patterns and modularity. This BGC is composed of three sections, two well-conserved right/left arms flanking a very variable middle section, composed of nrps genes. The presence of two non-canonical domains in H-CA8f’s BGC may contribute to adding chemical diversity to this family of NPs. Liquid chromatography-high resolution MS and dereplication efforts retrieved a set of related orphan metabolites, the corynecins, which to our knowledge are reported here for the first time in Rhodococcus . Overall, our data provide insights to connect BGC uniqueness with orphan metabolites, by revealing key comparative genomic features supported by models of BGC distribution along phylogeny.

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Section: Resultsmentioning

confidence: 99%

Rhodococcus comparative genomics reveals a phylogenomic-dependent non-ribosomal peptide synthetase distribution: insights into biosynthetic gene cluster connection to an orphan metabolite

et al. 2021

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“…Enzymatic reactivation of Cm by chloramphenicol acetate esterases that counteract the chloramphenicol acetyl transferase (CAT) activity has been reported previously. − A similar mechanism is probably responsible for the activity of P6L4 since the inset sequence had multiple ORFs with esterases as the predicted gene product (Supplemental Data 1). Three different esterases were predicted, including an esterase, a carboxylesterase, and a metallophosphoesterase (ORFs 12, 35, and 77, respectively; GenBank accession MF620030.1).…”

Section: Resultsmentioning

confidence: 61%

Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics

et al. 2018

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A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol ( Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acetyl-3-butanoylchloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol. Cm was used as the selectable antibiotic for cloning, suggesting that heterologously expressed enzymes resulted in derivatization of Cm into new chemical entities with biological activity. An esterase was found to be responsible for the enzymatic regeneration of Cm, and the gene trfA responsible for plasmid copy induction was found to be responsible for inducing antibacterial activity in some clones. Six additional acylchloramphenicols were synthesized for structure and antibacterial activity relationship studies, with 1- p-nitrobenzoylchloramphenicol the most active against Mycobacterium intracellulare and Mycobacterium tuberculosis, with MICs of 12.5 and 50.0 μg/mL, respectively.

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“…Chloramphenicol is a dichloro-substituted acetamide with broad-spectrum antibacterial activity [ 64 ]. Corynecin I is a chloramphenicol-like acyl-nitrophenylpropylamine that also has broad-spectrum antibacterial activity [ 65 , 66 ].…”

Section: Resultsmentioning

confidence: 99%

iChip-Inspired Isolation, Bioactivities and Dereplication of Actinomycetota from Portuguese Beach Sediments

et al. 2022

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Oceans hold a stunning number of unique microorganisms, which remain unstudied by culture-dependent methods due to failures in establishing the right conditions for these organisms to grow. In this work, an isolation effort inspired by the iChip was performed using marine sediments from Memoria beach, Portugal. The isolates obtained were identified by 16S rRNA gene analysis, fingerprinted using BOX-PCR and ERIC-PCR, searched for the putative presence of secondary metabolism genes associated with polyketide synthase I (PKS-I) and non-ribosomal peptide synthetases (NRPS), screened for antimicrobial activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, and had bioactive extracts dereplicated by LC/HRMS. Of the 158 isolated strains, 96 were affiliated with the phylum Actinomycetota, PKS-I and NRPS genes were detected in 53 actinomycetotal strains, and 11 proved to be bioactive (10 against E. coli, 1 against S. aureus and 1 against both pathogens). Further bioactivities were explored using an “one strain many compounds” approach, with six strains showing continued bioactivity and one showing a novel one. Extract dereplication showed the presence of several known bioactive molecules and potential novel ones in the bioactive extracts. These results indicate the use of the bacteria isolated here as sources of new bioactive natural products.

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Corynecin (chloramphenicol analogs) fermentation studies: Selective production of Corynecin I by Corynebacterium hydrocarboclastus grown on acetate

Cited by 12 publications

References 15 publications

Rhodococcus comparative genomics reveals a phylogenomic-dependent non-ribosomal peptide synthetase distribution: insights into biosynthetic gene cluster connection to an orphan metabolite

Rhodococcus comparative genomics reveals a phylogenomic-dependent non-ribosomal peptide synthetase distribution: insights into biosynthetic gene cluster connection to an orphan metabolite

Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics

iChip-Inspired Isolation, Bioactivities and Dereplication of Actinomycetota from Portuguese Beach Sediments

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