Spliceostatin hemiketal biosynthesis in
            <i>Burkholderia</i>
            spp. is catalyzed by an iron/α-ketoglutarate–dependent dioxygenase

Eustáquio, Alessandra S.; Janso, Jeffrey E.; Ratnayake, Anokha S.; O’Donnell, Christopher J; Koehn, Frank E.

doi:10.1073/pnas.1408300111

Cited by 63 publications

(97 citation statements)

References 49 publications

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“…Burkholderia rhizoxinica produced antitumor product rhizoxin (Partida‐Martinez and Hertweck ) and Burkholderia spp produced spliceostatin (Eustaquio et al. ) were also included. The compared siderophores include pyochelin and ornibactin.…”

Section: Methodsmentioning

confidence: 99%

Comparative genome‐wide analysis reveals that Burkholderia contaminans MS14 possesses multiple antimicrobial biosynthesis genes but not major genetic loci required for pathogenesis

et al. 2016

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Burkholderia contaminans MS14 shows significant antimicrobial activities against plant and animal pathogenic fungi and bacteria. The antifungal agent occidiofungin produced by MS14 has great potential for development of biopesticides and pharmaceutical drugs. However, the use of Burkholderia species as biocontrol agent in agriculture is restricted due to the difficulties in distinguishing between plant growth‐promoting bacteria and the pathogenic bacteria. The complete MS14 genome was sequenced and analyzed to find what beneficial and virulence‐related genes it harbors. The phylogenetic relatedness of B. contaminans MS14 and other 17 Burkholderia species was also analyzed. To research MS14′s potential virulence, the gene regions related to the antibiotic production, antibiotic resistance, and virulence were compared between MS14 and other Burkholderia genomes. The genome of B. contaminans MS14 was sequenced and annotated. The genomic analyses reveal the presence of multiple gene sets for antimicrobial biosynthesis, which contribute to its antimicrobial activities. BLAST results indicate that the MS14 genome harbors a large number of unique regions. MS14 is closely related to another plant growth‐promoting Burkholderia strain B. lata 383 according to the average nucleotide identity data. Moreover, according to the phylogenetic analysis, plant growth‐promoting species isolated from soils and mammalian pathogenic species are clustered together, respectively. MS14 has multiple antimicrobial activity‐related genes identified from the genome, but it lacks key virulence‐related gene loci found in the pathogenic strains. Additionally, plant growth‐promoting Burkholderia species have one or more antimicrobial biosynthesis genes in their genomes as compared with nonplant growth‐promoting soil‐isolated Burkholderia species. On the other hand, pathogenic species harbor multiple virulence‐associated gene loci that are not present in nonpathogenic Burkholderia species. The MS14 genome as well as Burkholderia species genome show considerable diversity. Multiple antimicrobial agent biosynthesis genes were identified in the genome of plant growth‐promoting species of Burkholderia. In addition, by comparing to nonpathogenic Burkholderia species, pathogenic Burkholderia species have more characterized homologs of the gene loci known to contribute to pathogenicity and virulence to plant and animals.

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Section: Methodsmentioning

confidence: 99%

Comparative genome‐wide analysis reveals that Burkholderia contaminans MS14 possesses multiple antimicrobial biosynthesis genes but not major genetic loci required for pathogenesis

et al. 2016

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“…In contrast, the first PKS modules contained numerous noncanonical features that made a functional assignment challenging. More detailed analysis revealed that the unusual domain series starting with KS2 (KS 0 -acyl carrier protein [ACP]-TE B -KS 0 -ACP-C) occurs in an almost identical sequence (KS 0 -ACP-ACP-TE B -KS 0 -ACP-C) in the spliceostatin and thailanstatin PKSs (59,60), where it was assigned to a Z double bond, a feature also found at the matching peloruside moiety (C4 to C5). Interestingly, all three PKSs contain members of a phylogenetically distinct group of internal TE-like domains, previously misannotated as a dehydratase (DH) in the spliceostatin PKS, for which we proposed the name TE B .…”

Section: Mycalamide a (1)mentioning

confidence: 99%

A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli

Rust

Helfrich

Freeman

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Bacterial specialized metabolites are increasingly recognized as important factors in animal–microbiome interactions: for example, by providing the host with chemical defenses. Even in chemically rich animals, such compounds have been found to originate from individual members of more diverse microbiomes. Here, we identified a remarkable case of a moderately complex microbiome in the sponge host Mycale hentscheli in which multiple symbionts jointly generate chemical diversity. In addition to bacterial pathways for three distinct polyketide families comprising microtubule-inhibiting peloruside drug candidates, mycalamide-type contact poisons, and the eukaryotic translation-inhibiting pateamines, we identified extensive biosynthetic potential distributed among a broad phylogenetic range of bacteria. Biochemical data on one of the orphan pathways suggest a previously unknown member of the rare polytheonamide-type cytotoxin family as its product. Other than supporting a scenario of cooperative symbiosis based on bacterial metabolites, the data provide a rationale for the chemical variability of M. hentscheli and could pave the way toward biotechnological peloruside production. Most bacterial lineages in the compositionally unusual sponge microbiome were not known to synthesize bioactive metabolites, supporting the concept that microbial dark matter harbors diverse producer taxa with as yet unrecognized drug discovery potential.

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“…Species belonging to this genus have been isolated from soil, water, plants, animals and humans. 14 Several investigations have shown that they are prolific producers of specialised metabolites, [15][16][17][18][19][20][21][22][23][24] and genome sequence analyses have highlighted their underexplored biosynthetic potential. 25 To date, pathogenic Burkholderia species have been reported to produce siderophores belonging to three distinct structural classes (ornibactins/malleobactins, pyochelin, and cepaciachelin; Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Discovery and biosynthesis of gladiochelins: unusual lipodepsipeptide siderophores fromBurkholderia gladioli

Dashti

Nakou

Mullins

et al. 2020

Preprint

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Burkholderia is a genus of diverse Gram-negative bacteria that includes several opportunistic pathogens. Siderophores, which transport iron from the environment into microbial cells, are important virulence factors in most pathogenic Burkholderia species. However, it is widely believed that Burkholderia gladioli, which can infect the lungs of cystic fibrosis (CF) sufferers, does not produce siderophores. B. gladioli BCC0238, isolated from the lung of a CF patient, produces two novel metabolites in a minimal medium containing glycerol and ribose as carbon sources. HPLC purification, followed by detailed spectroscopic analyses, identified these metabolites as unusual lipodepsipeptides containing a unique citrate-derived fatty acid and a rare dehydro-β-alanine residue. The absolute configurations of the amino acid residues in the two metabolites was elucidated using Marfey's method and the gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis. In-frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster, which was found in the genomes of most B. gladioli isolates, suggesting that its metabolic products play an important role in the growth and/or survival of the species. The Chrome Azurol S (CAS) assay showed the metabolites bind ferric iron and that this supresses their production when added to the growth medium. Moreover, a gene encoding a TonB-dependent ferric-siderophore receptor is adjacent to the biosynthetic genes. Together, these observations suggest that these metabolites likely function as siderophores in B. gladioli.

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Spliceostatin hemiketal biosynthesis in Burkholderia spp. is catalyzed by an iron/α-ketoglutarate–dependent dioxygenase

Cited by 63 publications

References 49 publications

Comparative genome‐wide analysis reveals that Burkholderia contaminans MS14 possesses multiple antimicrobial biosynthesis genes but not major genetic loci required for pathogenesis

Comparative genome‐wide analysis reveals that Burkholderia contaminans MS14 possesses multiple antimicrobial biosynthesis genes but not major genetic loci required for pathogenesis

A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli

Discovery and biosynthesis of gladiochelins: unusual lipodepsipeptide siderophores fromBurkholderia gladioli

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