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https://www.readbyqxmd.com/read/28809560/recombinant-macrocyclic-lanthipeptides-incorporating-non-canonical-amino-acids
#1
Claudio Zambaldo, Xiaozhou Luo, Angad P Mehta, Peter G Schultz
Nisin is a complex lanthipeptide that has broad spectrum antibacterial activity. In efforts to broaden the structural diversity of this ribosomally synthesized lantibiotic, we now report the recombinant expression of Nisin variants that incorporate noncanonical amino acids (ncAAs) at discrete positions. This is achieved by expressing the nisA structural gene, cyclase (nisC) and dehydratase (nisB), together with an orthogonal nonsense suppressor tRNA/aminoacyl-tRNA synthetase pair in Escherichia coli. A number of ncAAs with novel chemical reactivity were genetically incorporated into NisA, including an α-chloroacetamide-containing ncAA that allowed for the expression of Nisin variants with novel macrocyclic topologies...
August 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28710266/specificity-of-subtilin-mediated-activation-of-histidine-kinase-spak
#2
Christoph Geiger, Tobias Spieß, Sophie Marianne Korn, Peter Kötter, Karl-Dieter Entian
Autoinduction via two-component systems is a widespread regulatory mechanism that senses environmental and metabolic changes. Although the lantibiotics nisin and subtilin are closely related and share the same lanthionine ring structure, they autoinduce their biosynthesis in a highly specific manner. Subtilin can only activate the two-component system SpaRK of Bacillus subtilis, whereas nisin activates solely the two-component system NisRK of Lactococcus lactis To identify components that determine the specificity of subtilin autoinduction, several variants of the respective lantibiotic were analyzed for their autoinduction capacity...
July 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28695849/full-length-nisin-immunity-protein-nisi-from-lactococcus-lactis-in-a-lipid-free-form-crystallization-and-x-ray-analysis
#3
Jin Hee Jeong, Sung Chul Ha
NisI is a lantibiotic-binding lipoprotein that is specific for nisin. Nisin-producing microorganisms use NisI as an immunity protein for self-protection against nisin. Here, the purification, crystallization and preliminary X-ray diffraction of full-length NisI from Lactobacillus lactis in a lipid-free form (NisI22-C) are reported. Importantly, reductive methylation of the lysine residues in NisI22-C was essential for initial crystallization. Only methylated NisI22-C crystallized. The optimized crystals of methylated NisI22-C were grown in 30-40 mM ammonium sulfate, 0...
July 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28675292/substrate-specificity-of-the-secreted-nisin-leader-peptidase-nisp
#4
Marcel Lagedroste, Sander H J Smits, Lutz Schmitt
Nisin (NisA) is an antimicrobial peptide produced by Lactococcus lactis and belongs to the class of lanthipeptides, more specifically to the class of lantibiotics. They are ribosomally synthesized as a precursor peptide and are comprised of an N-terminal leader peptide and a C-terminal core peptide. The core peptide is post-translationally modified and contains dehydrated amino acids in addition to five (methyl)-lanthionine rings, which are crucial for its activity. The leader peptide serves as a signal sequence and ensures that NisA remains inactive but secretion-competent within the cell...
August 1, 2017: Biochemistry
https://www.readbyqxmd.com/read/28659619/nano-engineering-the-antimicrobial-spectrum-of-lantibiotics-activity-of-nisin-against-gram-negative-bacteria
#5
Marija Vukomanović, Vojka Žunič, Špela Kunej, Boštjan Jančar, Samo Jeverica, Rok Podlipec, Danilo Suvorov
Lantibiotics, bacteria-sourced antimicrobial peptides, are very good candidates for effective and safe food additives. Among them, nisin is already approved by the EU and FDA, and has been used in food preservation for the past 40 years. Now, there is a possibility and strong interest to extend its applicability to biomedicine for designing innovative alternatives to antibiotics. The main obstacle is, however, its naturally narrow spectrum of antimicrobial activity, focused on Gram positive bacteria. Here we demonstrate broadening nisin's spectrum to Gram negative bacteria using a nano-engineering approach...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28654661/structure-dynamics-and-kinetics-of-two-component-lantibiotic-lichenicidin
#6
Alejandra de Miguel, Rafael Tapia-Rojo, Tillmann Utesch, Maria Andrea Mroginski
Two variants of the two-component Lantibiotic Lichenicidin, produced by the strains B. Licheniformis VK21 and I89 (Lchα/ Lchβ and Bliα/ Bliβ peptides, respectively) have been investigated by means of 2 μs-long all-atom molecular dynamics simulations combined with Markov State Models. This rigorous statistical analysis enabled to evaluate the dynamic and kinetic properties of the aforementioned systems which are not accessible via experimental techniques. The structural flexibility characteristic of these small peptides is understood by a delicate equilibrium between random coil, α-helices and β-sheet structures...
2017: PloS One
https://www.readbyqxmd.com/read/28583849/rapid-detection-of-lactococcuslactis-isolates-producing-the-lantibiotics-nisin-lacticin-481-and-lacticin-3147-using-maldi-tof-ms
#7
Tomás García-Cayuela, Teresa Requena, M Carmen Martínez-Cuesta, Carmen Peláez
The aim of the study was to evaluate the potential use of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for fast and reliable detection of strains producing the lantibiotics nisin, lacticin 481 and lacticin 3147 in a large collection of lactococci. A total of one hundred lactococcal isolates from traditional ewe's and goat's raw milk cheeses were identified to the species level as Lactococcuslactis by MALDI-TOF MS based on comparison with lactococcal entries in the BioTyper database...
June 2, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28579477/two-highly-divergent-lineages-of-exfoliative-toxin-b-encoding-plasmids-revealed-in-impetigo-strains-of-staphylococcus-aureus
#8
Tibor Botka, Vladislava Růžičková, Karla Svobodová, Roman Pantůček, Petr Petráš, Darina Čejková, Jiří Doškař
Exfoliative toxin B (ETB) encoded by some large plasmids plays a crucial role in epidermolytic diseases caused by Staphylococcus aureus. We have found as yet unknown types of etb gene-positive plasmids isolated from a set of impetigo strains implicated in outbreaks of pemphigus neonatorum in Czech maternity hospitals. Plasmids from the strains of clonal complex CC121 were related to archetypal plasmid pETBTY4. Sharing a 33-kb core sequence including virulence genes for ETB, EDIN C, and lantibiotics, they were assigned to a stand-alone lineage, named pETBTY4-based plasmids...
May 29, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28576760/mathermycin-a-lantibiotic-from-the-marine-actinomycete-marinactinospora-thermotolerans-scsio-00652
#9
Erquan Chen, Qi Chen, Shaoming Chen, Bing Xu, Jianhua Ju, Huan Wang
Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from Marinactinospora thermotolerans SCSIO 00652 and reconstituted its biosynthesis in Streptomyces lividans and Escherichia coli Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from Marinactinospora species...
August 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28500042/carboxyl-analogue-of-mutacin-1140-a-scaffold-for-lead-antibacterial-discovery
#10
Jerome Escano, Akshaya Ravichandran, Bita Salamat, Leif Smith
Mutacin 1140 belongs to the epidermin group of lantibiotics. Epidermin class lantibiotics are ribosomally synthesized and posttranslationally modified antibiotics with potent activity against Gram-positive bacteria. In particular, this class is effective at targeting drug-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, and Clostridium difficile A C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) residue is derived from a decarboxylation of a terminal cysteine that is involved in lanthionine ring formation...
July 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28462050/a-profile-hidden-markov-model-to-investigate-the-distribution-and-frequency-of-lanb-encoding-lantibiotic-modification-genes-in-the-human-oral-and-gut-microbiome
#11
Calum J Walsh, Caitriona M Guinane, Paul W O' Toole, Paul D Cotter
BACKGROUND: The human microbiota plays a key role in health and disease, and bacteriocins, which are small, bacterially produced, antimicrobial peptides, are likely to have an important function in the stability and dynamics of this community. Here we examined the density and distribution of the subclass I lantibiotic modification protein, LanB, in human oral and stool microbiome datasets using a specially constructed profile Hidden Markov Model (HMM). METHODS: The model was validated by correctly identifying known lanB genes in the genomes of known bacteriocin producers more effectively than other methods, while being sensitive enough to differentiate between different subclasses of lantibiotic modification proteins...
2017: PeerJ
https://www.readbyqxmd.com/read/28362216/strategies-for-combating-bacterial-biofilms-a-focus-on-anti-biofilm-agents-and-their-mechanisms-of-action
#12
Ranita Roy, Monalisa Tiwari, Gianfranco Donelli, Vishvanath Tiwari
Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity...
March 31, 2017: Virulence
https://www.readbyqxmd.com/read/28352561/synergistic-effect-of-haloduracin-and-chloramphenicol-against-clinically-important-gram-positive-bacteria
#13
Abolghasem Danesh, Åsa Ljungh, Bo Mattiasson, Gashaw Mamo
The emergence of drug-resistant pathogens has triggered the search for more efficient antimicrobial agents and formulations for treatment of infections. In recent years, combination therapy has become one of the effective clinical practices in treating infections. The present study deals with the effect of haloduracin, a lantibiotic bateriocin and chloramphenicol against clinically important bacteria. The combined use of haloduracin and chloramphenicol resulted in remarkable synergy against a spectrum of microorganisms including strains of Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis and different groups of Streptococcus...
March 2017: Biotechnology Reports
https://www.readbyqxmd.com/read/28306363/genome-database-mining-for-the-discovery-of-novel-lantibiotics
#14
REVIEW
Stephanie K Sandiford
The effectiveness of lantibiotics against MDR pathogens and the progression of agents MU1140, NAI-107, NVB302 and duramycin into pre-clinical and clinical trials have highlighted their potential in the fight against bacterial resistance. The number of known lantibiotics and knowledge of their biosynthetic pathways has increased in recent years due to higher quality genomic data being delivered by next generation sequencing technologies combined with the development of specific genome mining tools, enabling the prediction of lantibiotic clusters...
May 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28294058/recognizing-and-predicting-thioether-bridges-formed-by-lanthionine-and-%C3%AE-methyllanthionine-in-lantibiotics-using-a-random-forest-approach-with-feature-selection
#15
ShaoPeng Wang, Yu-Hang Zhang, Ning Zhang, Lei Chen, Tao Huang, Yu-Dong Cai
Lantibiotics, which are usually produced from Gram-positive bacteria, are regarded as one type of special bacteriocins. Lantibiotics have unsaturated amino acid residues formed by lanthionine (Lan) and β-methyllanthionine (MeLan) residues as a ring structure in the peptide. They are derived from the serine and threonine residues and are essential to preventing the growth of other similar strains. In this pioneering work, we firstly proposed a machine learning method to recognize and predict the Lan and MeLan residues in the protein sequences of lantibiotics...
March 10, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28285660/genetic-and-biochemical-characterization-of-hyicin-3682-the-first-bacteriocin-reported-for-staphylococcus-hyicus
#16
Patrícia Carlin Fagundes, Ilana Nascimento de Sousa Santos, Márcia Silva Francisco, Rodolpho Mattos Albano, Maria do Carmo de Freire Bastos
Hyicin 3682, the first bacteriocin reported for Staphylococcus hyicus, is a BsaCOL variant produced by S. hyicus 3682, a strain isolated from bovine milk. Hyicin 3682 is found in the culture supernatant, is bactericidal and its producing strain exhibits a much broader spectrum of antimicrobial activity than the producing strain of BsaCOL against several Gram-positive bacteria, which include foodborne pathogens, food-spoilage microorganisms and bacterial species of medical and veterinary importance. Sequencing of the genome of S...
May 2017: Microbiological Research
https://www.readbyqxmd.com/read/28270262/lantibiotics-produced-by-actinobacteria-and-their-potential-applications-a-review
#17
Karen Machado Gomes, Rafael Silva Duarte, Maria do Carmo de Freire Bastos
The phylum Actinobacteria, which comprises a great variety of Gram-positive bacteria with a high G+C content in their genomes, is known for its large production of bioactive compounds, including those with antimicrobial activity. Among the antimicrobials, bacteriocins, ribosomally synthesized peptides, represent an important arsenal of potential new drugs to face the increasing prevalence of resistance to antibiotics among microbial pathogens. The actinobacterial bacteriocins form a heterogeneous group of substances that is difficult to adapt to most proposed classification schemes...
February 2017: Microbiology
https://www.readbyqxmd.com/read/28235608/the-complete-genome-sequence-of-bacillus-velezensis-9912d-reveals-its-biocontrol-mechanism-as-a-novel-commercial-biological-fungicide-agent
#18
Hua-Qi Pan, Qing-Lian Li, Jiang-Chun Hu
A Bacillus sp. 9912 mutant, 9912D, was approved as a new biological fungicide agent by the Ministry of Agriculture of the People's Republic of China in 2016 owing to its excellent inhibitory effect on various plant pathogens and being environment-friendly. Here, we present the genome of 9912D with a circular chromosome having 4436 coding DNA sequences (CDSs), and a circular plasmid encoding 59 CDSs. This strain was finally designated as Bacillus velezensis based on phylogenomic analyses. Genome analysis revealed a total of 19 candidate gene clusters involved in secondary metabolite biosynthesis, including potential new type II lantibiotics...
April 10, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28184221/identification-of-key-residues-in-the-nisk-sensor-region-for-nisin-biosynthesis-regulation
#19
Xiaoxuan Ge, Kunling Teng, Jian Wang, Fangyuan Zhao, Jie Zhang, Jin Zhong
Histidine kinase (HK) NisK is well known to sense lantibiotic nisin for regulating the biosynthesis of nisin. NisK possesses two trans-membrane segments and a large extracellular region and nisin contains 34 amino acids with five lanthionine rings. Unlike most peptide sensing HK with multi trans-membrane segments, NisK is a representative of a group of rarely reported HK that sense peptide as ligand. To reveal how NisK senses nisin molecule to regulate nisin biosynthesis, we constructed a reporter Lactococcus lactis strain with nisRK constitutively expressed and a reporter gene lacZ expressed under the control of promoter P nisA ...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28169337/stoichiometry-and-structure-of-a-lantibiotic-maturation-complex
#20
Jens Reiners, André Abts, Rebecca Clemens, Sander H J Smits, Lutz Schmitt
Lantibiotics are ribosomally synthesized antimicrobial peptides secreted by mainly Gram-positive bacteria. Class 1 lantibiotics mature via two modification steps introduced by a modification LanBC complex. For the lantibiotic nisin, the dehydratase NisB catalyzes the dehydration of serine and threonine residues in the so-called core peptide. Second, five (methyl)-lanthionine rings are introduced in a regio- and stereospecific manner by the cyclase NisC. Here, we characterized the assembly of the NisBC complex in vitro, which is only formed in the presence of the substrate...
February 7, 2017: Scientific Reports
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