scholarly journals Genome-Guided Discovery of the First Myxobacterial Biarylitide Myxarylin Reveals Distinct C–N Biaryl Crosslinking in RiPP Biosynthesis

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7483
Author(s):  
Joachim J. Hug ◽  
Nicolas A. Frank ◽  
Christine Walt ◽  
Petra Šenica ◽  
Fabian Panter ◽  
...  
Keyword(s):  
Amino Acids ◽  
Myxococcus Xanthus ◽  
Aromatic Amino Acids ◽  
Diverse Group ◽  
Guided Discovery ◽  
Post Translational Modifications ◽  
Wide Range ◽  
Genomic Analyses ◽  
Modified Peptides ◽  
In Silico Analyses

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse group of natural products. They feature a wide range of intriguing post-translational modifications, as exemplified by the biarylitides. These are a family of cyclic tripeptides found in Planomonospora, carrying a biaryl linkage between two aromatic amino acids. Recent genomic analyses revealed that the minimal biosynthetic prerequisite of biarylitide biosynthesis consists of only one ribosomally synthesized pentapeptide precursor as the substrate and a modifying cytochrome-P450-dependent enzyme. In silico analyses revealed that minimal biarylitide RiPP clusters are widespread among natural product producers across phylogenetic borders, including myxobacteria. We report here the genome-guided discovery of the first myxobacterial biarylitide MeYLH, termed Myxarylin, from Pyxidicoccus fallax An d48. Myxarylin was found to be an N-methylated tripeptide that surprisingly exhibits a C–N biaryl crosslink. In contrast to Myxarylin, previously isolated biarylitides are N-acetylated tripeptides that feature a C–C biaryl crosslink. Furthermore, the formation of Myxarylin was confirmed by the heterologous expression of the identified biosynthetic genes in Myxococcus xanthus DK1622. These findings expand the structural and biosynthetic scope of biarylitide-type RiPPs and emphasize the distinct biochemistry found in the myxobacterial realm.

scholarly journals Genome-guided Discovery of the First Myxobacterial Biarylitide Myxarylin Reveals Distinct C–N Biaryl Crosslinking in RiPP Biosynthesis

2021 ◽  
Author(s):  
Joachim J. Hug ◽  
Nicolas A. Frank ◽  
Christine Walt ◽  
Petra Šenica ◽  
Fabian Panter ◽  
...  
Keyword(s):  
Amino Acids ◽  
Posttranslational Modifications ◽  
Myxococcus Xanthus ◽  
Aromatic Amino Acids ◽  
Diverse Group ◽  
Guided Discovery ◽  
Wide Range ◽  
Genomic Analyses ◽  
Modified Peptides ◽  
In Silico Analyses

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse group of natural products. They feature a wide range of intriguing posttranslational modifications as exemplified by the biarylitides. These are a family of cyclic tripeptides found in Planomonospora, carrying a biaryl-linkage between two aromatic amino acids. Recent genomic analyses revealed the minimal biosynthetic prerequisite of biarylitide biosynthesis consisting of only one ribosomally synthesized pentapeptide precursor as substrate and a modifying cytochrome P450 dependent enzyme. In silico analyses revealed that the minimal biarylitide RiPP clusters are widespread among natural product producers across phylogenetic borders including myxobacteria. We report here the genome-guided discovery of the first myxobacterial biarylitide MeYLH termed Myxarylin from Pyxidicoccus fallax An d48. Myxarylin was found to be an N-methylated tripeptide surprisingly exhibiting a C–N biaryl crosslink. In contrast to Myxarylin, previously isolated biarylitides are N-acetylated tripeptides featuring a C–C biaryl crosslink. Furthermore, the formation of Myxarylin was confirmed by heterologous expression of the identified biosynthetic genes in Myxococcus xanthus DK1622. These findings expand the structural and biosynthetic scope of biarylitide type RiPPs and emphasize the distinct biochemistry found in the myxobacterial realm.

Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity

2002 ◽  
Vol 80 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Morten B Strøm ◽  
Bengt Erik Haug ◽  
Øystein Rekdal ◽  
Merete L Skar ◽  
Wenche Stensen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Structural Parameters ◽  
Aromatic Amino Acids ◽  
Structural Features ◽  
Tryptophan Residue ◽  
Qsar Study ◽  
Modified Peptides ◽  
Bovine Lactoferricin ◽  
Derivatives Of

This review focuses on important structural features affecting the antimicrobial activity of 15-residue derivatives of lactoferricins. Our investigations are based on an alanine-scan of a 15-residue bovine lactoferricin derivative that revealed the absolute necessity of two tryptophan residues for antimicrobial activity. This "tryptophan-effect" was further explored in homologous derivatives of human, caprine, and porcine lactoferricins by the incorporation of one additional tryptophan residue, and by increasing the content of tryptophan in the bovine derivative to five residues. Most of the resulting peptides display a substantial increase in antimicrobial activity. To identify which molecular properties make tryptophan so effective, a series of bovine lactoferricin derivatives were prepared containing non-encoded unnatural aromatic amino acids, which represented various aspects of the physicochemical nature of tryptophan. The results clearly demonstrate that tryptophan is not unique since most of the modified peptides were of higher antimicrobial potency than the native peptide. The size and three-dimensional shape of the inserted "super-tryptophans" are the most important determinants for the high antimicrobial activity of the modified peptides. This review also describes the use of a "soft-modeling" approach in order to identify important structural parameters affecting the antimicrobial activity of modified 15-residue murine lactoferricin derivatives. This QSAR-study revealed that the net charge, charge asymmetry, and micelle affinity of the peptides were the most important structural parameters affecting their antimicrobial activity.Key words: antimicrobial peptides, lactoferricin, non-encoded aromatic amino acids, tryptophan.

scholarly journals Enhanced Production of Aromatic Amino Acids in Tobacco Plants Leads to Increased Phenylpropanoid Metabolites and Tolerance to Stresses

2021 ◽  
Vol 11 ◽  
Author(s):  
Moran Oliva ◽  
Aviv Guy ◽  
Gad Galili ◽  
Evgenia Dor ◽  
Ron Schweitzer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Transgenic Plants ◽  
Morphological Changes ◽  
Protein A ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
High Accumulation ◽  
Bacterial Gene ◽  
Enhanced Production ◽  
Wide Range

Aromatic amino acids (AAAs) synthesized in plants via the shikimate pathway can serve as precursors for a wide range of secondary metabolites that are important for plant defense. The goals of the current study were to test the effect of increased AAAs on primary and secondary metabolic profiles and to reveal whether these plants are more tolerant to abiotic stresses (oxidative, drought and salt) and to Phelipanche egyptiaca (Egyptian broomrape), an obligate parasitic plant. To this end, tobacco (Nicotiana tabacum) plants were transformed with a bacterial gene (AroG) encode to feedback-insensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, the first enzyme of the shikimate pathway. Two sets of transgenic plants were obtained: the first had low expression of the AroG protein, a normal phenotype and minor metabolic changes; the second had high accumulation of the AroG protein with normal, or deleterious morphological changes having a dramatic shift in plant metabolism. Metabolic profiling analysis revealed that the leaves of the transgenic plants had increased levels of phenylalanine (up to 43-fold), tyrosine (up to 24-fold) and tryptophan (up to 10-fold) compared to control plants having an empty vector (EV) and wild type (WT) plants. The significant increase in phenylalanine was accompanied by higher levels of metabolites that belong to the phenylpropanoid pathway. AroG plants showed improved tolerance to salt stress but not to oxidative or drought stress. The most significant improved tolerance was to P. aegyptiaca. Unlike WT/EV plants that were heavily infected by the parasite, the transgenic AroG plants strongly inhibited P. aegyptiaca development, and only a few stems of the parasite appeared above the soil. This delayed development of P. aegyptiaca could be the result of higher accumulation of several phenylpropanoids in the transgenic AroG plants and in P. aegyptiaca, that apparently affected its growth. These findings indicate that high levels of AAAs and their related metabolites have the potential of controlling the development of parasitic plants.

The Efficient Preparation of Radiolabeled Aromatic Amino Acids via Cu-Mediated Radiofluorination using Ni-complexes

2019 ◽  
Author(s):  
A Craig ◽  
N Kolks ◽  
E Urusova ◽  
BD Zlatopolskiy ◽  
B Neumaier
Keyword(s):  
Amino Acids ◽  
Aromatic Amino Acids

Long term dietary intake of aromatic amino acids are associated with leptin gene expression in adipose tissues of non-diabetic adults

2018 ◽  
Author(s):  
Golaleh Asghari ◽  
Emad Yuzbashian ◽  
Maryam Zarkesh ◽  
Parvin Mirmiran ◽  
Mehdi Hedayati ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Dietary Intake ◽  
Aromatic Amino Acids ◽  
Adipose Tissues

Single Amino Acid Based Self-Assemblies of Cysteine and Methionine

2018 ◽  
Author(s):  
Nidhi Gour ◽  
Bharti Koshti ◽  
Chandra Kanth P. ◽  
Dhruvi Shah ◽  
Vivek Shinh Kshatriya ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Self Assembly ◽  
Aromatic Amino Acids ◽  
Neutral Condition ◽  
Single Amino Acid ◽  
Binding Assays ◽  
Human Neuroblastoma ◽  
Cytotoxicity Assays ◽  
First Time

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. To get insights into the structure formation, thioflavin T and Congo red binding assays were done which revealed that aggregates may not have amyloid like characteristics. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. The cytotoxicity assays of cysteine and methionine structures were performed on Human Neuroblastoma IMR-32 cells which suggested that aggregates are not cytotoxic in nature and thus, may not have amyloid like etiology. The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.

Atypical amino acids inhibit histidine, valine, or lysine transport into rat brain

1983 ◽  
Vol 245 (4) ◽  
pp. R556-R563 ◽  
Author(s):  
J. K. Tews ◽  
A. E. Harper
Keyword(s):  
Amino Acids ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
Brain Slices ◽  
Aromatic Amino Acids ◽  
Brain Barrier ◽  
Basic Amino Acids ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Single Meal

Transport of histidine, valine, or lysine into rat brain slices and across the blood-brain barrier (BBB) was determined in the presence of atypical nonprotein amino acids. Competitors of histidine and valine transport in slices were large neutral amino acids including norleucine, norvaline, alpha-aminooctanoate, beta-methylphenylalanine, and alpha-aminophenylacetate. Less effective were aromatic amino acids with ring substituents; ineffective were basic amino acids and omega-amino isomers of norleucine and aminooctanoate. Lysine transport was moderately depressed by homoarginine or ornithine plus arginine; large neutral amino acids were also similarly inhibitory. Histidine or valine transport across the BBB was also strongly inhibited by large neutral amino acids that were the most effective competitors in the slices (norvaline, norleucine, alpha-aminooctanoate, and alpha-aminophenylacetate); homoarginine and 8-aminooctanoate were ineffective. Homoarginine, ornithine, and arginine almost completely blocked lysine transport, but the large neutral amino acids were barely inhibitory. When rats were fed a single meal containing individual atypical large neutral amino acids or homoarginine, brain pools of certain large neutral amino acids or of arginine and lysine, respectively, were depleted.

scholarly journals Yeast TKL1 gene encodes a transketolase that is required for efficient glycolysis and biosynthesis of aromatic amino acids.

1993 ◽  
Vol 268 (32) ◽  
pp. 24346-24352
Author(s):  
M Sundström ◽  
Y Lindqvist ◽  
G Schneider ◽  
U Hellman ◽  
H Ronne
Keyword(s):  
Amino Acids ◽  
Aromatic Amino Acids
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