An environmental bacterial taxon with a large and distinct metabolic repertoire

Wilson, Micheal C.; Mori, Tetsushi; Rückert, Christian; Uria, Agustinus Robert; Helf, Maximilian J.; Takada, Kentaro; Gernert, Christine; Steffens, Ursula A. E.; Heycke, Nina; Schmitt, Susanne; Rinke, Christian; Helfrich, Eric J. N.; Brachmann, Alexander O.; Gurgui, Cristian; Wakimoto, Toshiyuki; Kracht, Matthias; Crüsemann, Max; Hentschel, Ute; Abe, Ikuro; Matsunaga, Shigeki; Kalinowski, Jörn; Takeyama, Haruko; Piel, Jörn

doi:10.1038/nature12959

Cited by 522 publications

(583 citation statements)

References 68 publications

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“…In addition, cof genes were disproportionally abundant in known soil-and marine-dwelling orders of Proteobacteria (for example, Rhizobiales and Alteromonadales) compared with host-associated orders (for example, Rickettsiales and Enterobacteriales) (Supplementary Table S1). Finally, F 420 biosynthesis genes were also detected in two Firmicutes species and within the Tectomicrobia (Supplementary Table S3), a recently discovered candidate phylum with wide biosynthetic capacity (Wilson et al, 2014). Putative F 420 -dependent oxidoreductases from multiple families were identified in the genomes of the phyla predicted to synthesize F 420 (Supplementary Table S4).…”

Section: Resultsmentioning

confidence: 99%

The methanogenic redox cofactor F420 is widely synthesized by aerobic soil bacteria

et al. 2016

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F 420 is a low-potential redox cofactor that mediates the transformations of a wide range of complex organic compounds. Considered one of the rarest cofactors in biology, F 420 is best known for its role in methanogenesis and has only been chemically identified in two phyla to date, the Euryarchaeota and Actinobacteria. In this work, we show that this cofactor is more widely distributed than previously reported. We detected the genes encoding all five known F 420 biosynthesis enzymes (cofC, cofD, cofE, cofG and cofH) in at least 653 bacterial and 173 archaeal species, including members of the dominant soil phyla Proteobacteria, Chloroflexi and Firmicutes. Metagenome datamining validated that these genes were disproportionately abundant in aerated soils compared with other ecosystems. We confirmed through high-performance liquid chromatography analysis that aerobically grown stationary-phase cultures of three bacterial species, Paracoccus denitrificans, Oligotropha carboxidovorans and Thermomicrobium roseum, synthesized F 420 , with oligoglutamate sidechains of different lengths. To understand the evolution of F 420 biosynthesis, we also analyzed the distribution, phylogeny and genetic organization of the cof genes. Our data suggest that although the F o precursor to F 420 originated in methanogens, F 420 itself was first synthesized in an ancestral actinobacterium. F 420 biosynthesis genes were then disseminated horizontally to archaea and other bacteria. Together, our findings suggest that the cofactor is more significant in aerobic bacterial metabolism and soil ecosystem composition than previously thought. The cofactor may confer several competitive advantages for aerobic soil bacteria by mediating their central metabolic processes and broadening the range of organic compounds they can synthesize, detoxify and mineralize.

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Section: Resultsmentioning

confidence: 99%

The methanogenic redox cofactor F420 is widely synthesized by aerobic soil bacteria

et al. 2016

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“…An intriguing example is represented by the single‐cell and metagenomics‐based approach leading to the identification of the novel bacterial taxon ‘ Entotheonella ’ that co‐inhabits the Red sea marine sponge Theonella swinhoei . Metagenomic analysis showed that more than 40 bioactive polyketides and modified peptides belonging to seven different structural classes are produced by the endosymbiont in association with the sponge (Wilson et al ., 2014). …”

Section: Novel Approaches For Drug Discoverymentioning

confidence: 99%

Antibiotic drug discovery

Wohlleben

Mast

Stegmann

et al. 2016

Microbial Biotechnology

122

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SummaryDue to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a ‘New Age of Antibiotic Discovery’. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years.

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“…Mature bottromycins ( 1 – 5 , Figure 2) were clearly absent in every mutant, but the complexity of the data hampered the detailed characterization of metabolites. Therefore, this was followed by mass spectral network analysis,18 which is a powerful tool that identifies similarities in MS 2 fragmentation data and builds a network of species with related MS 2 spectra, thus identifying structurally‐related molecules within a complex mixture 18, 19, 20, 21, 22, 23, 24. This has been used to assess the global metabolic profiles of a single organism, either in isolation19 or when interacting with neighboring species,18 to compare the metabolomes of related organisms,20, 21, 22 to assess the metabolic potential of a new bacterial taxon,23 and to identify metabolites related to the colibactin pathway 24…”

mentioning

confidence: 99%

Dissecting Bottromycin Biosynthesis Using Comparative Untargeted Metabolomics

et al. 2016

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Bottromycin A2 is a structurally unique ribosomally synthesized and post‐translationally modified peptide (RiPP) that possesses potent antibacterial activity towards multidrug‐resistant bacteria. The structural novelty of bottromycin stems from its unprecedented macrocyclic amidine and rare β‐methylated amino acid residues. The N‐terminus of a precursor peptide (BtmD) is converted into bottromycin A2 by tailoring enzymes encoded in the btm gene cluster. However, little was known about key transformations in this pathway, including the unprecedented macrocyclization. To understand the pathway in detail, an untargeted metabolomic approach that harnesses mass spectral networking was used to assess the metabolomes of a series of pathway mutants. This analysis has yielded key information on the function of a variety of previously uncharacterized biosynthetic enzymes, including a YcaO domain protein and a partner protein that together catalyze the macrocyclization.

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An environmental bacterial taxon with a large and distinct metabolic repertoire

Cited by 522 publications

References 68 publications

The methanogenic redox cofactor F420 is widely synthesized by aerobic soil bacteria

The methanogenic redox cofactor F420 is widely synthesized by aerobic soil bacteria

Antibiotic drug discovery

Dissecting Bottromycin Biosynthesis Using Comparative Untargeted Metabolomics

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