The kleboxymycin biosynthetic gene cluster is encoded by several species belonging to the Klebsiella oxytoca complex

ABSTRACTAs part of ongoing studies with clinically relevant Klebsiella spp., we characterized the genomes of three clinical GES-5-positive strains originally identified as Klebsiella oxytoca. Average nucleotide identity and phylogenetic analyses showed the strains to be Klebsiella michiganensis. In addition to encoding GES-5, the strains encoded SHV-66, a β-lactamase not previously identified in K. michiganensis. The strains further encoded a range of virulence factors and the kleboxymycin biosynthetic gene cluster (BGC), previously only found in K. oxytoca strains and one strain of Klebsiella grimontii. This BGC, associated with antibiotic-associated haemorrhagic colitis, has not previously been reported in K. michiganensis, and this finding led us to carry out a wide-ranging study to determine the prevalence of this BGC in Klebsiella spp. Of 7,170 publicly available Klebsiella genome sequences screened, 88 encoded the kleboxymycin BGC. All BGC-positive strains belonged to the K. oxytoca complex, with strains of four (K. oxytoca, K. pasteurii, K. grimontii, K. michiganensis) of the six species of the complex found to encode the complete BGC. In addition to being found in K. grimontii strains isolated from preterm infants, the BGC was found in K. oxytoca and K. michiganensis metagenome-assembled genomes recovered from neonates. Detection of the kleboxymycin BGC across the K. oxytoca complex may be of clinical relevance and this cluster should be included in databases characterizing virulence factors, in addition to those characterizing BGCs.Data statementSupplementary data associated with this article are available from figshare.Data summaryDraft genome sequences for PS_Koxy1, PS_Koxy2 and PS_Koxy4 have been deposited with links to BioProject accession number PRJNA562720 in the NCBI BioProject database.IMPACT STATEMENTExtended analyses of the genomes of Klebsiella spp. have revealed the kleboxymycin biosynthetic gene cluster (BGC) is restricted to species of the Klebsiella oxytoca complex (K. oxytoca, K. michiganensis, K. pasteurii and K. grimontii). Species- and/or gene-specific differences in the cluster’s sequences may be relevant to virulence of K. oxytoca and related species. The finding of the kleboxymycin BGC in the preterm infant gut microbiota may have implications for disease presentation in a subset of neonates.

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Improved molecular characterization of the Klebsiella oxytoca complex reveals the prevalence of the kleboxymycin biosynthetic gene cluster

Microbial Genomics ◽

10.1099/mgen.0.000592 ◽

2021 ◽

Vol 7 (6) ◽

Author(s):

Preetha Shibu ◽

Frazer McCuaig ◽

Anne L. McCartney ◽

Magdalena Kujawska ◽

Lindsay J. Hall ◽

...

Keyword(s):

Gene Cluster ◽

Type Species ◽

Phylogenetic Analyses ◽

Klebsiella Oxytoca ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Genome Sequences ◽

Content Type ◽

Link Type

As part of the ongoing studies with clinically relevant Klebsiella spp., we characterized the genomes of three clinical GES-5-positive ST138 strains originally identified as Klebsiella oxytoca. bla OXY gene, average nucleotide identity and phylogenetic analyses showed the strains to be Klebsiella michiganensis . Affiliation of the strains to ST138 led us to demonstrate that the current multi-locus sequence typing scheme for K. oxytoca can be used to distinguish members of this genetically diverse complex of bacteria. The strains encoded the kleboxymycin biosynthetic gene cluster (BGC), previously only found in K. oxytoca strains and one strain of Klebsiella grimontii . The finding of this BGC, associated with antibiotic-associated haemorrhagic colitis, in K. michiganensis led us to carry out a wide-ranging study to determine the prevalence of this BGC in Klebsiella spp. Of 7170 publicly available Klebsiella genome sequences screened, 88 encoded the kleboxymycin BGC. All BGC-positive strains belonged to the K. oxytoca complex, with strains of four ( K. oxytoca , K. pasteurii , K. grimontii , K. michiganensis ) of the six species of complex found to encode the complete BGC. In addition to being found in K. grimontii strains isolated from preterm infants, the BGC was found in K. oxytoca and K. michiganensis metagenome-assembled genomes recovered from neonates. Detection of the kleboxymycin BGC across the K. oxytoca complex may be of clinical relevance and this cluster should be included in databases characterizing virulence factors, in addition to those characterizing BGCs.

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Characterization of the Nodularin Synthetase Gene Cluster and Proposed Theory of the Evolution of Cyanobacterial Hepatotoxins

Applied and Environmental Microbiology ◽

10.1128/aem.70.11.6353-6362.2004 ◽

2004 ◽

Vol 70 (11) ◽

pp. 6353-6362 ◽

Cited By ~ 169

Author(s):

Michelle C. Moffitt ◽

Brett A. Neilan

Keyword(s):

Gene Cluster ◽

Rational Design ◽

Polyketide Synthase ◽

Alternative Hypothesis ◽

Phylogenetic Analyses ◽

Cyanobacterial Bloom ◽

Gene Clusters ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Microcystin Synthetase

ABSTRACT Nodularia spumigena is a bloom-forming cyanobacterium which produces the hepatotoxin nodularin. The complete gene cluster encoding the enzymatic machinery required for the biosynthesis of nodularin in N. spumigena strain NSOR10 was sequenced and characterized. The 48-kb gene cluster consists of nine open reading frames (ORFs), ndaA to ndaI, which are transcribed from a bidirectional regulatory promoter region and encode nonribosomal peptide synthetase modules, polyketide synthase modules, and tailoring enzymes. The ORFs flanking the nda gene cluster in the genome of N. spumigena strain NSOR10 were identified, and one of them was found to encode a protein with homology to previously characterized transposases. Putative transposases are also associated with the structurally related microcystin synthetase (mcy) gene clusters derived from three cyanobacterial strains, indicating a possible mechanism for the distribution of these biosynthetic gene clusters between various cyanobacterial genera. We propose an alternative hypothesis for hepatotoxin evolution in cyanobacteria based on the results of comparative and phylogenetic analyses of the nda and mcy gene clusters. These analyses suggested that nodularin synthetase evolved from a microcystin synthetase progenitor. The identification of the nodularin biosynthetic gene cluster and evolution of hepatotoxicity in cyanobacteria reported in this study may be valuable for future studies on toxic cyanobacterial bloom formation. In addition, an appreciation of the natural evolution of nonribosomal biosynthetic pathways will be vital for future combinatorial engineering and rational design of novel metabolites and pharmaceuticals.

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Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics The GenBank accession number for the sequence of cosmid K1F2 is AF329398.

Microbiology ◽

10.1099/00221287-148-12-3901 ◽

2002 ◽

Vol 148 (12) ◽

pp. 3901-3911 ◽

Cited By ~ 100

Author(s):

Florence Pojer ◽

Shu-Ming Li ◽

Lutz Heide

Keyword(s):

Sequence Analysis ◽

Molecular Cloning ◽

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Accession Number

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Genome-based characterization of a plasmid-associated micrococcin P1 biosynthetic gene cluster and virulence factors in Mammaliicoccus sciuri IMDO-S72

Applied and Environmental Microbiology ◽

10.1128/aem.02088-21 ◽

2021 ◽

Author(s):

David Van der Veken ◽

Charlie Hollanders ◽

Marko Verce ◽

Chris Michiels ◽

Steven Ballet ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gene Cluster ◽

Virulence Factors ◽

Resistance Genes ◽

De Novo ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Genetic Elements

Analysis of the de novo assembled genome of Mammaliicoccus sciuri IMDO-S72 revealed the genetically encoded machinery behind its earlier reported antibacterial phenotype and gave further insight into the repertoire of putative virulence factors of this recently reclassified species. A plasmid-encoded biosynthetic gene cluster was held responsible for the antimicrobial activity of M. sciuri IMDO-S72, comprising genes involved in thiopeptide production. The compound encoded by this gene cluster was structurally identified as micrococcin P1. Further examination of its genome highlighted the ubiquitous presence of innate virulence factors mainly involved in surface colonization. Determinants contributing to aggressive virulence were generally absent, with exception of a plasmid-associated ica cluster. The native antibiotic resistance genes sal (A) and mecA were detected within the genome, amongst others, but were not consistently linked with a resistant phenotype. While mobile genetic elements were identified within the genome, such as an untypeable SCC element, they proved to be generally free of virulence- and antibiotic-related genes. These results further suggest a commensal lifestyle of M. sciuri and indicate the association of antibiotic resistance determinants with mobile genetic elements, as an important factor in conferring antibiotic resistance, in addition to their unilateral annotation. Importance Mammaliicoccus sciuri has been put forward as an important carrier of virulence and antibiotic resistance genes, which can be transmitted to clinically important staphylococcal species such as Staphylococcus aureus . As a common inhabitant of mammal skin, this species is believed to have a predominant commensal lifestyle although it has been reported as an opportunistic pathogen in some cases. This study provides an extensive genome-wide description of its putative virulence potential taking into consideration the genomic context in which these genes appear, an aspect that is often overlooked during virulence analysis. Additional genome and biochemical analysis linked M. sciuri with the production of micrococcin P1, gaining further insight to which extent these biosynthetic gene cluster are distributed amongst different related species. The frequent plasmid-associated character hints that these traits can be horizontally transferred and might confer a competitive advantage to its recipient within its ecological niche.

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Draft genome sequence of Streptomyces coelicoflavus ZG0656 reveals the putative biosynthetic gene cluster of acarviostatin family α-amylase inhibitors

Letters in Applied Microbiology ◽

10.1111/j.1472-765x.2012.03274.x ◽

2012 ◽

Vol 55 (2) ◽

pp. 162-169 ◽

Cited By ~ 14

Author(s):

X. Guo ◽

P. Geng ◽

F. Bai ◽

G. Bai ◽

T. Sun ◽

...

Keyword(s):

Gene Cluster ◽

Genome Sequence ◽

Draft Genome ◽

Biosynthetic Gene Cluster ◽

Draft Genome Sequence ◽

Biosynthetic Gene ◽

Amylase Inhibitors

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High-Quality Draft Genome Sequence of the Actinobacterium Nocardia terpenica IFM 0406, Producer of the Immunosuppressant Brasilicardins, Using Illumina and PacBio Technologies

Genome Announcements ◽

10.1128/genomea.01391-16 ◽

2016 ◽

Vol 4 (6) ◽

Cited By ~ 6

Author(s):

Anina Buchmann ◽

Michael Eitel ◽

Pierre Koch ◽

Paul N. Schwarz ◽

Evi Stegmann ◽

...

Keyword(s):

Secondary Metabolites ◽

Heterologous Expression ◽

Gene Cluster ◽

Genome Sequence ◽

Draft Genome ◽

Biosynthetic Gene Cluster ◽

Draft Genome Sequence ◽

Biosynthetic Gene ◽

High Quality

The bacterium Nocardia terpenica IFM 0406 is known as the producer of the immunosuppressant brasilicardin A. Here, we report the completely sequenced genome of strain IFM 0406, which facilitates the heterologous expression of the brasilicardin biosynthetic gene cluster but also unveils the intriguing biosynthetic capacity of the strain to produce secondary metabolites.

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Draft Genome Sequence of the Novonestmycin-Producing Strain Streptomyces sp. Z26, Isolated from Potato Rhizosphere in Morocco

Microbiology Resource Announcements ◽

10.1128/mra.01514-18 ◽

2019 ◽

Vol 8 (1) ◽

Author(s):

Anina Buchmann ◽

Carolina Cano-Prieto ◽

Ahmed Nafis ◽

Mustapha Barakate ◽

Mohamed Baz ◽

...

Keyword(s):

Antifungal Activity ◽

Secondary Metabolites ◽

Gene Cluster ◽

Draft Genome ◽

Production Capacity ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Content Type ◽

Streptomyces Sp ◽

Insight Into

Streptomyces sp. strain Z26 exhibited antifungal activity and turned out to be a producer of the secondary metabolites novonestmycin A and B. The 6.5-Mb draft genome gives insight into the complete secondary metabolite production capacity and builds the basis to find and locate the biosynthetic gene cluster encoding the novonestmycins.

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Draft Genome Sequence of Linfuranone Producer Microbispora sp. GMKU 363

Genome Announcements ◽

10.1128/genomea.01471-15 ◽

2015 ◽

Vol 3 (6) ◽

Cited By ~ 5

Author(s):

Hisayuki Komaki ◽

Natsuko Ichikawa ◽

Akira Hosoyama ◽

Nobuyuki Fujita ◽

Arinthip Thamchaipenet ◽

...

Keyword(s):

Gene Cluster ◽

Genome Sequence ◽

Polyketide Synthase ◽

Adipocyte Differentiation ◽

Draft Genome ◽

Biosynthetic Gene Cluster ◽

Draft Genome Sequence ◽

Biosynthetic Gene

Here, we report the draft genome sequence of Microbispora sp. GMKU 363, a plant-derived actinomycete that produces linfuranone A, a linear polyketide modified with a furanone ring possessing adipocyte differentiation inducing activity. The biosynthetic gene cluster for linfuranone was identified by analyzing polyketide synthase genes in the genome.

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Cloning and analysis of the spinosad biosynthetic gene cluster of Saccharopolyspora spinosa11The DNA sequence reported here was deposited in GenBank under the accession number AY007564.

Chemistry & Biology ◽

10.1016/s1074-5521(01)00029-1 ◽

2001 ◽

Vol 8 (5) ◽

pp. 487-499 ◽

Cited By ~ 141

Author(s):

Clive Waldron ◽

Patti Matsushima ◽

Paul R Rosteck ◽

Mary C Broughton ◽

Jan Turner ◽

...

Keyword(s):

Gene Cluster ◽

Dna Sequence ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Accession Number

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Anacyclamide D8P, a prenylated cyanobactin from a Sphaerospermopsis sp. cyanobacterium

10.26434/chemrxiv.5346739.v1 ◽

2017 ◽

Cited By ~ 1

Author(s):

Joana Martins ◽

Niina Leikoski ◽

Matti Wahlsten ◽

Joana Azevedo ◽

Jorge Antunes ◽

...

Keyword(s):

Gene Cluster ◽

Cyclic Peptides ◽

Biosynthetic Gene Cluster ◽

The Novel ◽

Tyrosine Residue ◽

Biosynthetic Gene ◽

Post Translational Modification ◽

Biological Assays ◽

Mass Spectrometric Data ◽

Spectrometric Data

Cyanobactins are a family of linear and cyclic peptides produced through the post-translational modification of short precursor peptides. Anacyclamides are macrocyclic cyanobactins with a highly diverse sequence that are common in the genus Anabaena. A mass spectrometry-based screening of potential cyanobactin producers led to the discovery of a new prenylated member of this family of compounds, anacyclamide D8P (1), from Sphaerospermopsis sp. LEGE 00249. The anacyclamide biosynthetic gene cluster (acy) encoding the novel macrocyclic prenylated cyanobactin, was sequenced. Heterologous expression of the acy gene cluster in Escherichia coli established the connection between genomic and mass spectrometric data. Unambiguous establishment of the type and site of prenylation required the full structural elucidation of 1 using Nuclear Magnetic Resonance (NMR), which demonstrated that a forward prenylation occurred on the tyrosine residue. Compound 1 was tested in pharmacologically or ecologically relevant biological assays and revealed moderate antimicrobial activity towards the fouling bacterium Halomonas aquamarina CECT 5000.

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