Dataset Information

Engineering of a Peptide α-N-Methyltransferase to Methylate Non-Proteinogenic Amino Acids.

ABSTRACT: Introduction of α-N-methylated non-proteinogenic amino acids into peptides can improve their biological activities, membrane permeability and proteolytic stability. This is commonly achieved, in nature and in the lab, by assembling pre-methylated amino acids. The more appealing route of methylating amide bonds is challenging. Biology has evolved an α-N-automethylating enzyme, OphMA, which acts on the amide bonds of peptides fused to its C-terminus. Due to the ribosomal biosynthesis of its substrate, the activity of this enzyme towards peptides with non-proteinogenic amino acids has not been addressed. An engineered OphMA, intein-mediated protein ligation and solid-phase peptide synthesis have allowed us to demonstrate the methylation of amide bonds in the context of non-natural amides. This approach may have application in the biotechnological production of therapeutic peptides.

SUBMITTER: Song H

PROVIDER: S-EPMC8251615 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Engineering of a Peptide α-N-Methyltransferase to Methylate Non-Proteinogenic Amino Acids.

Song Haigang H Burton Antony J AJ Shirran Sally L SL Fahrig-Kamarauskaitė Jūratė J Kaspar Hannelore H Muir Tom W TW Künzler Markus M Naismith James H JH

Angewandte Chemie (International ed. in English) 20210517 26

Introduction of α-N-methylated non-proteinogenic amino acids into peptides can improve their biological activities, membrane permeability and proteolytic stability. This is commonly achieved, in nature and in the lab, by assembling pre-methylated amino acids. The more appealing route of methylating amide bonds is challenging. Biology has evolved an α-N-automethylating enzyme, OphMA, which acts on the amide bonds of peptides fused to its C-terminus. Due to the ribosomal biosynthesis of its substr ...[more]

PMID: 33856715

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Project description:Circulating blood is an important plasma free amino acids (PFAAs) reservoir and a pivotal link between metabolic pathways. No comparisons are available between athletes with opposite training adaptations that include a broader spectrum of both proteinogenic and non-proteinogenic amino acids, and that take into account skeletal muscle mass. We hypothesized that the levels of the exercise-induced PFAAs concentration are related to the type of training-related metabolic adaptation. We compared highly trained endurance athletes (n = 11) and sprinters (n = 10) aged 20‒35 years who performed incremental exercise until exhaustion. Venous blood was collected before and during the test and 30-min recovery (12 samples). Forty-two PFAAs were assayed using LC-ESI-MS/MS technique. Skeletal muscle mass was estimated using dual X-ray absorptiometry method. Glutamine and alanine were dominant PFAAs throughout the whole exercise and recovery period (~350‒650 μmol∙L-1). Total, combined proteinogenic, non-essential, and non-proteinogenic PFAAs levels were significantly higher in endurance athletes than sprinters (ANOVA group effects: p = 0.007, η2 = 0.321; p = 0.011, η2 = 0.294; p = 0.003, η2 = 0.376; p = 0.001, η2 = 0.471, respectively). The exercise response was more pronounced in endurance athletes, especially for non-proteinogenic PFAAs (ANOVA interaction effect: p = 0.038, η2 = 0.123). Significant between-group differences were observed for 19 of 33 PFAAs detected, including 4 essential, 7 non-essential, and 8 non-proteinogenic ones. We demonstrated that the PFAAs response to incremental aerobic exercise is associated with the type of training-related metabolic adaptation. A greater turnover and availability of circulating PFAAs for skeletal muscles and other body tissues is observed in endurance- than in sprint-trained individuals. Non-proteinogenic PFAAs, despite low concentrations, also respond to exercise loads, indicating their important, though less understood role in exercise metabolism. Our study provides additional insight into the exercise-induced physiological response of PFAAs, and may also provide a rationale in discussions regarding dietary amino acid requirements in high-performance athletes with respect to sports specialization.

Dataset Information

Engineering of a Peptide α-N-Methyltransferase to Methylate Non-Proteinogenic Amino Acids.

Publications

Engineering of a Peptide α-N-Methyltransferase to Methylate Non-Proteinogenic Amino Acids.

Similar Datasets

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