cblaster: a remote search tool for rapid identification and visualisation of homologous gene clusters

Gilchrist, Cameron L.M.; Booth, Thomas; Chooi, Yit‐Heng

doi:10.1101/2020.11.08.370601

Cited by 17 publications

(21 citation statements)

References 47 publications

(54 reference statements)

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“…To gain insight into the function of the minor parent BGC, the sequences of Orf6595 and proteins encoded by the surrounding genes were searched against the MIBiG database 44 using cblaster 45 . The search identified the BGC as homologous to the rimosamide (rmo) BGC from Streptomyces rimosus ATCC 10970 46 (Supplementary Table 10).…”

Section: Biochemical Validation Of A-domain Substrate Specificitiesmentioning

confidence: 99%

Bifurcation drives the evolution of assembly-line biosynthesis

Kaj

Liston

et al. 2021

Preprint

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Reprogramming biosynthetic assembly-lines is a topic of intense interest. This is unsurprising as the scaffolds of most antibiotics in current clinical use are produced by such pathways. The modular nature of assembly-lines provides a direct relationship between the sequence of enzymatic domains and the chemical structure of the product, but rational reprogramming efforts have been met with limited success. To gain greater insight into the design process, we wanted to examine how Nature creates assembly-lines and searched for biosynthetic pathways that might represent evolutionary transitions. By examining the biosynthesis of the anti-tubercular wollamides, we show how whole gene duplication and neofunctionalization can result in pathway bifurcation. Importantly, we show that neofunctionalization occurs primarily through intragenomic recombination. This pathway bifurcation leads to redundancy, providing the genetic robustness required to enable large structural changes during the evolution of antibiotic structures. Should the new product be none-functional, gene loss can restore the original genotype. However, if the new product confers an advantage, depreciation and eventual loss of the original gene creates a new linear pathway. This provides the blind watchmaker equivalent to the design, build, test cycle of synthetic biology.

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Section: Biochemical Validation Of A-domain Substrate Specificitiesmentioning

confidence: 99%

Bifurcation drives the evolution of assembly-line biosynthesis

Kaj

Liston

et al. 2021

Preprint

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“…To pursue other BGCs for tolyporphins that resemble BGC-1 in strain HT-58-2, further analysis of genomic data of the HT-58-2 cyanobacterium and comparative genomics of other filamentous cyanobacteria were conducted using the sequence of BGC-1 as a query ( Figure 1 ) [ 13 ]. We used manual BLASTP database searching, rather than more automated methods similar to AntiSMASH [ 33 ], MultiGeneBlast [ 34 ], and cblaster [ 35 ] since the definitive role of tolyporphins BGCs has not been established, nor has the HT-58-2 BGC-1 been incorporated into commonly utilized BGC search engines. While our focus was to look outward to other organisms, we unexpectedly found a second, less extensive putative tolyporphins BGC (termed BGC-2) in HT-58-2 at region 2,994,941–3,043,548 bp.…”

Section: Resultsmentioning

confidence: 99%

Identification of Putative Biosynthetic Gene Clusters for Tolyporphins in Multiple Filamentous Cyanobacteria

Jin

Zhang

et al. 2021

Life

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Tolyporphins A–R are unusual tetrapyrrole macrocycles produced by the non-axenic filamentous cyanobacterium HT-58-2. A putative biosynthetic gene cluster for biosynthesis of tolyporphins (here termed BGC-1) was previously identified in the genome of HT-58-2. Here, homology searching of BGC-1 in HT-58-2 led to identification of similar BGCs in seven other filamentous cyanobacteria, including strains Nostoc sp. 106C, Nostoc sp. RF31YmG, Nostoc sp. FACHB-892, Brasilonema octagenarum UFV-OR1, Brasilonema octagenarum UFV-E1, Brasilonema sennae CENA114 and Oculatella sp. LEGE 06141, suggesting their potential for tolyporphins production. A similar gene cluster (BGC-2) also was identified unexpectedly in HT-58-2. Tolyporphins BGCs were not identified in unicellular cyanobacteria. Phylogenetic analysis based on 16S rRNA and a common component of the BGCs, TolD, points to a close evolutionary history between each strain and their respective tolyporphins BGC. Though identified with putative tolyporphins BGCs, examination of pigments extracted from three cyanobacteria has not revealed the presence of tolyporphins. Overall, the identification of BGCs and potential producers of tolyporphins presents a collection of candidate cyanobacteria for genetic and biochemical analysis pertaining to these unusual tetrapyrrole macrocycles.

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“…The biosynthetic gene cluster for both the ambigols ( ab ) and tjipanazoles ( tjp ) were recently characterised by Duell et al, [ 17 ] and Chilczuk et al, [ 18 ], respectively. To determine if other organisms may have the genetic capability to produce these molecules, we performed a bioinformatic screening across all genomes within the NCBI database using cblaster [ 56 ]. This revealed that currently the ab or tpj gene clusters cannot be found in any organism other than Symphyonema bifilamentata sp.…”

Section: Discussionmentioning

confidence: 99%

Symphyonema bifilamentata sp. nov., the Right Fischerella ambigua 108b: Half a Decade of Research on Taxonomy and Bioactive Compounds in New Light

et al. 2021

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Since 1965 a cyanobacterial strain termed ‘Fischerella ambigua 108b’ was the object of several studies investigating its potential as a resource for new bioactive compounds in several European institutes. Over decades these investigations uncovered several unique small molecules and their respective biosynthetic pathways, including the polychlorinated triphenyls of the ambigol family and the tjipanazoles. However, the true taxonomic character of the producing strain remained concealed until now. Applying a polyphasic approach considering the phylogenetic position based on the 16S rRNA and the protein coding gene rbcLX, secondary structures and morphological features, we present the strain ‘Fischerella ambigua 108b’ as Symphyonema bifilamentata sp. nov. 97.28. Although there is the type species (holotype) S. sinense C.-C. Jao 1944 there is no authentic living strain or material for genetic analyses for the genus Symphyonema available. Thus we suggest and provide an epitypification of S. bifilamentata sp. nov. 97.28 as a valid reference for the genus Symphyonema. Its affiliation to the family Symphyonemataceae sheds not only new light on this rare taxon but also on the classes of bioactive metabolites of these heterocytous and true-branching cyanobacteria which we report here. We show conclusively that the literature on the isolation of bioactive products from this organism provides further support for a clear distinction between the secondary metabolism of Symphyonema bifilamentata sp. nov. 97.28 compared to related and other taxa, pointing to the assignment of this organism into a separate genus.

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cblaster: a remote search tool for rapid identification and visualisation of homologous gene clusters

Cited by 17 publications

References 47 publications

Bifurcation drives the evolution of assembly-line biosynthesis

Bifurcation drives the evolution of assembly-line biosynthesis

Identification of Putative Biosynthetic Gene Clusters for Tolyporphins in Multiple Filamentous Cyanobacteria

Symphyonema bifilamentata sp. nov., the Right Fischerella ambigua 108b: Half a Decade of Research on Taxonomy and Bioactive Compounds in New Light

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