scholarly journals New Insight into Antimicrobial Compounds from Food and Marine-Sourced Carnobacterium Species through Phenotype and Genome Analyses

2020 ◽  
Vol 8 (7) ◽  
pp. 1093
Author(s):  
Simon Begrem ◽  
Flora Ivaniuk ◽  
Frédérique Gigout-Chevalier ◽  
Laetitia Kolypczuk ◽  
Sandrine Bonnetot ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Biosynthetic Gene Cluster ◽  
Ecological Niches ◽  
Antimicrobial Compounds ◽  
Biosynthetic Gene ◽  
Peptide Synthetase ◽  
Seafood Products ◽  
Genome Analyses ◽  
Encoding Genes ◽  
Insight Into

Carnobacterium maltaromaticum and Carnobacterium divergens, isolated from food products, are lactic acid bacteria known to produce active and efficient bacteriocins. Other species, particularly those originating from marine sources, are less studied. The aim of the study is to select promising strains with antimicrobial potential by combining genomic and phenotypic approaches on large datasets comprising 12 Carnobacterium species. The biosynthetic gene cluster (BGCs) diversity of 39 publicly available Carnobacterium spp. genomes revealed 67 BGCs, distributed according to the species and ecological niches. From zero to six BGCs were predicted per strain and classified into four classes: terpene, NRPS (non-ribosomal peptide synthetase), NRPS-PKS (hybrid non-ribosomal peptide synthetase-polyketide synthase), RiPP (ribosomally synthesized and post-translationally modified peptide). In parallel, the antimicrobial activity of 260 strains from seafood products was evaluated. Among the 60% of active strains, three genomes were sequenced and submitted to a dereplication process. C. inhibens MIP2551 produced a high amountof H2O2, probably thanks to the presence of four oxidase-encoding genes. C. maltaromaticum EBP3019 and SF668 strains were highly efficient against Listeria monocytogenes. A new extracellular 16 kDa unmodified bacteriocin in the EBP3019 strain and five different bacteriocins in SF668 were highlighted. In this study, the overview of antimicrobial BGC and inhibitory activities of Carnobacterium spp. allowed the prediction of potential innovative natural products that could be relevant for biotechnological applications.

scholarly journals Characterization of a Gene Cluster Responsible for the Biosynthesis of Anticancer Agent FK228 in Chromobacterium violaceum No. 968

2007 ◽  
Vol 73 (11) ◽  
pp. 3460-3469 ◽  
Author(s):  
Yi-Qiang Cheng ◽  
Min Yang ◽  
Andrea M. Matter
Keyword(s):  
Gene Cluster ◽  
Genomic Dna ◽  
Polyketide Synthase ◽  
Anticancer Agent ◽  
Biosynthetic Gene Cluster ◽  
Nonribosomal Peptide Synthetase ◽  
Biosynthetic Gene ◽  
Biosynthetic Genes ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase

ABSTRACT A gene cluster responsible for the biosynthesis of anticancer agent FK228 has been identified, cloned, and partially characterized in Chromobacterium violaceum no. 968. First, a genome-scanning approach was applied to identify three distinctive C. violaceum no. 968 genomic DNA clones that code for portions of nonribosomal peptide synthetase and polyketide synthase. Next, a gene replacement system developed originally for Pseudomonas aeruginosa was adapted to inactivate the genomic DNA-associated candidate natural product biosynthetic genes in vivo with high efficiency. Inactivation of a nonribosomal peptide synthetase-encoding gene completely abolished FK228 production in mutant strains. Subsequently, the entire FK228 biosynthetic gene cluster was cloned and sequenced. This gene cluster is predicted to encompass a 36.4-kb DNA region that includes 14 genes. The products of nine biosynthetic genes are proposed to constitute an unusual hybrid nonribosomal peptide synthetase-polyketide synthase-nonribosomal peptide synthetase assembly line including accessory activities for the biosynthesis of FK228. In particular, a putative flavin adenine dinucleotide-dependent pyridine nucleotide-disulfide oxidoreductase is proposed to catalyze disulfide bond formation between two sulfhydryl groups of cysteine residues as the final step in FK228 biosynthesis. Acquisition of the FK228 biosynthetic gene cluster and acclimation of an efficient genetic system should enable genetic engineering of the FK228 biosynthetic pathway in C. violaceum no. 968 for the generation of structural analogs as anticancer drug candidates.

scholarly journals Biosynthetic Gene Cluster for the Polyenoyltetramic Acid α-Lipomycin

2006 ◽  
Vol 50 (6) ◽  
pp. 2113-2121 ◽  
Author(s):  
C. Bihlmaier ◽  
E. Welle ◽  
C. Hofmann ◽  
K. Welzel ◽  
A. Vente ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Biosynthetic Gene Cluster ◽  
Open Reading Frames ◽  
Biosynthetic Gene ◽  
Peptide Synthetases ◽  
Insight Into ◽  
Reading Frames ◽  
Module System

ABSTRACT The gram-positive bacterium Streptomyces aureofaciens Tü117 produces the acyclic polyene antibiotic α-lipomycin. The entire biosynthetic gene cluster (lip gene cluster) was cloned and characterized. DNA sequence analysis of a 74-kb region revealed the presence of 28 complete open reading frames (ORFs), 22 of them belonging to the biosynthetic gene cluster. Central to the cluster is a polyketide synthase locus that encodes an eight-module system comprised of four multifunctional proteins. In addition, one ORF shows homology to those for nonribosomal peptide synthetases, indicating that α-lipomycin belongs to the classification of hybrid peptide-polyketide natural products. Furthermore, the lip cluster includes genes responsible for the formation and attachment of d-digitoxose as well as ORFs that resemble those for putative regulatory and export functions. We generated biosynthetic mutants by insertional gene inactivation. By analysis of culture extracts of these mutants, we could prove that, indeed, the genes involved in the biosynthesis of lipomycin had been cloned, and additionally we gained insight into an unusual biosynthesis pathway.

scholarly journals Biosynthesis of Mycotoxin Fusaric Acid and Application of a PLP-Dependent Enzyme for Chemoenzymatic Synthesis of Substituted L-Pipecolic Acids

2020 ◽  
Author(s):  
Yang Hai ◽  
Mengbin Chen ◽  
Arthur Huang ◽  
Yi Tang
Keyword(s):  
Biosynthetic Pathway ◽  
Polyketide Synthase ◽  
Picolinic Acid ◽  
Fusaric Acid ◽  
Biosynthetic Gene Cluster ◽  
Chemoenzymatic Synthesis ◽  
Flavin Mononucleotide ◽  
Biosynthetic Gene ◽  
Bond Forming ◽  
Peptide Synthetase

<div><p>Fusaric acid (FA) is a well-known mycotoxin that plays an important role in plant pathology. The biosynthetic gene cluster for FA has been identified but the biosynthetic pathway remains unclarified. Here, we elucidated the biosynthesis of FA, which features a two-enzyme catalytic cascade, a pyridoxal 5’-phosphate (PLP)-dependent enzyme (Fub7) and a flavin mononucleotide (FMN)-dependent oxidase (Fub9) in synthesizing the picolinic acid scaffold. FA biosynthesis also involves an off-line collaboration between a highly reducing polyketide synthase (HRPKS, Fub1) and a nonribosomal peptide synthetase (NRPS)-like carboxylic acid reductase (Fub8) in making an aliphatic alpha,beta-unsaturated aldehyde. By harnessing the stereoselective C-C bond forming activity of Fub7, we established a chemoenzymatic route for stereoconvergent synthesis of a series of 5-alkyl, 5,5-dialkyl, and 5,5,6-trialkyl-L-pipecolic acids of high diastereomeric ratio. </p></div>

scholarly journals Shared PKS modules in biosynthesis of synergistic laxaphycins

2020 ◽  
Author(s):  
LMP Heinilä ◽  
DP Fewer ◽  
J Jokela ◽  
M Wahlsten ◽  
A Jortikka ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Polyketide Synthase ◽  
Biosynthetic Gene Cluster ◽  
Future Research ◽  
Biosynthetic Pathways ◽  
Biosynthetic Gene ◽  
Wide Range ◽  
Peptide Synthetase ◽  
Antiproliferative Activities

AbstractCyanobacteria produce a wide range of lipopeptides that exhibit potent membrane-disrupting activities. Laxaphycins consist of two families of structurally distinct macrocyclic lipopeptides that act in a synergistic manner to produce antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here, we identified the biosynthetic pathways responsible for the biosynthesis of the laxaphycins produced by Scytonema hofmannii PCC 7110. We show that these laxaphycins, called scytocyclamides, are produced by this cyanobacterium and are encoded in a single biosynthetic gene cluster with shared polyketide synthase enzymes initiating two distinct non-ribosomal peptide synthetase pathways. To our knowledge, laxaphycins are the first clearly distinct polyketide synthase and non-ribosomal peptide synthetase hybrid natural products with shared branched biosynthesis. The unusual mechanism of shared enzymes synthesizing two distinct types of products may aid future research in identifying and expressing natural product biosynthetic pathways and in expanding the known biosynthetic logic of this important family of natural products.

scholarly journals Biosynthesis of Mycotoxin Fusaric Acid and Application of a PLP-Dependent Enzyme for Chemoenzymatic Synthesis of Substituted L-Pipecolic Acids

2020 ◽  
Author(s):  
Yang Hai ◽  
Mengbin Chen ◽  
Arthur Huang ◽  
Yi Tang
Keyword(s):  
Biosynthetic Pathway ◽  
Polyketide Synthase ◽  
Picolinic Acid ◽  
Fusaric Acid ◽  
Biosynthetic Gene Cluster ◽  
Chemoenzymatic Synthesis ◽  
Flavin Mononucleotide ◽  
Biosynthetic Gene ◽  
Bond Forming ◽  
Peptide Synthetase

<div><p>Fusaric acid (FA) is a well-known mycotoxin that plays an important role in plant pathology. The biosynthetic gene cluster for FA has been identified but the biosynthetic pathway remains unclarified. Here, we elucidated the biosynthesis of FA, which features a two-enzyme catalytic cascade, a pyridoxal 5’-phosphate (PLP)-dependent enzyme (Fub7) and a flavin mononucleotide (FMN)-dependent oxidase (Fub9) in synthesizing the picolinic acid scaffold. FA biosynthesis also involves an off-line collaboration between a highly reducing polyketide synthase (HRPKS, Fub1) and a nonribosomal peptide synthetase (NRPS)-like carboxylic acid reductase (Fub8) in making an aliphatic alpha,beta-unsaturated aldehyde. By harnessing the stereoselective C-C bond forming activity of Fub7, we established a chemoenzymatic route for stereoconvergent synthesis of a series of 5-alkyl, 5,5-dialkyl, and 5,5,6-trialkyl-L-pipecolic acids of high diastereomeric ratio. </p></div>

scholarly journals Pentaminomycins F and G, First Non-Ribosomal Peptides Containing 2-Pyridylalanine

2020 ◽  
Author(s):  
Daniel Carretero Molina ◽  
Francisco Javier Ortiz-Lopez ◽  
Jesús Martín ◽  
Ignacio González ◽  
Marina Sánchez-Hidalgo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acid ◽  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Peptide Synthetase ◽  
Non Ribosomal Peptides

Pentaminomycins F-H, a group of three new hydroxyarginine-containing cyclic pentapeptides, were isolated from cultures of a <i>Streptomyces cacaoi</i> subsp. <i>cacaoi</i> strain along with the known pentaminomycins A-E. The structures of the new peptides were determined by a combination of mass spectrometry and NMR and Marfey's analyses. Among them, pentaminomycins F and G were shown to contain in their structures the rare amino acid 3-(2-pyridyl)-alanine. This finding represents the first reported example of non-ribosomal peptides containing this residue. The LDLLD chiral sequence found for the three compounds was in agreement with that reported for previously isolated pentaminomycins and consistent with the epimerization domains present in the putative non-robosomal peptide synthetase (NRPS) biosynthetic gene cluster.<br>

Biosynthesis of the uridine-derived nucleoside antibiotic A-94964: identification and characterization of the biosynthetic gene cluster provide insight into the biosynthetic pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 461-466 ◽  
Author(s):  
Taro Shiraishi ◽  
Makoto Nishiyama ◽  
Tomohisa Kuzuyama
Keyword(s):  
Gene Cluster ◽  
In Silico ◽  
Biosynthetic Pathway ◽  
Gene Deletion ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Identification And Characterization ◽  
Insight Into

The biosynthetic pathway of the uridine-derived nucleoside antibiotic A-94964 was proposed via in silico analysis coupled with gene deletion experiments.

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