Amino acid profile and scores of some selected traditional diets commonly consumed in northwest zone, Nigeria

Background and aims: Amino acids composition of local and regional dietary proteins determines the protein quality. The study was aimed at evaluating amino acid profiles of some selected traditional diets commonly consumed in Jigawa (JG), Kano (KN) and Katsina (KT) States, Northwest Zone-Nigeria. Methods: The selected prepared diets (four per state) include; JG Tuwon masara using white maize served with Kuka soup (JG TMW SWKS), JG Tuwon masara using yellow maize served with Kuka soup (JG TMY SWKS), JG Danwake served with groundnut oil and pepper (JG Danwake SWGOP), JG Moimoi, KN Tuwon masara using white maize served with Kuka soup (KN TMW SWKS), KN Tuwon masara using yellow maize served with Kuka soup (KN TMY SWKS), KN rice and beans served with groundnut oil and pepper (KN Rice and Beans SWGOP), KN Danwake served with groundnut oil and pepper (KN Danwake SWGOP), KT Tuwon masara using white maize served with Kuka soup (KT TMW SWKS), KT Tuwon masara using yellow maize served with Kuka soup (KT TMY SWKS), KT Danwake served with groundnut oil and pepper (KT Danwake SWGOP) and KT Dambu. The preparations were dried and grounded into powdered form and analyzed using standard methods. Results: The amino acid profile of the diets consumed in the three states show higher content of total non-essential amino acids (NEAA) compared with essential amino acids (EAA). The amino acid score of the prepared diets though higher than the standard amino acid score by WHO/FAO/UNU (2007), may support the normal growth of all age groups except lysine. The limiting amino acid score was found to be either lysine or SAA (cysteine + methionine) in all the 3 states’ diets. Histidine was found to have the highest score in all the diets except in JG Moimoi and KN Danwake served with groundnut oil and pepper (SWGOP) respectively. The low levels of lysine and SAA in some of the diets may be due to low contents of these amino acids in the ingredients used. Conclusion: This study showed that, the amino acid score of the prepared diets though higher than the standard amino acid score established by WHO/FAO/UNU may support the normal growth of infants, children as well as adults except lysine. Keywords: traditional diets, amino acids, amino acid profile, amino acid score.

Evolution as a Guide to Designing xeno Amino Acid Alphabets

Here, we summarize a line of remarkably simple, theoretical research to better understand the chemical logic by which life’s standard alphabet of 20 genetically encoded amino acids evolved. The connection to the theme of this Special Issue, “Protein Structure Analysis and Prediction with Statistical Scoring Functions”, emerges from the ways in which current bioinformatics currently lacks empirical science when it comes to xenoproteins composed largely or entirely of amino acids from beyond the standard genetic code. Our intent is to present new perspectives on existing data from two different frontiers in order to suggest fresh ways in which their findings complement one another. These frontiers are origins/astrobiology research into the emergence of the standard amino acid alphabet, and empirical xenoprotein synthesis.

A Novel Lipopeptaibol Emericellipsin A with Antimicrobial and Antitumor Activity Produced by the Extremophilic Fungus Emericellopsis alkalina

Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies.

Software-aided workflow for predicting protease-specific cleavage sites using physicochemical properties of the natural and unnatural amino acids in peptide-based drug discovery: Peptide cleavage sites prediction workflow

Peptide drugs have been used in the treatment of multiple pathologies. During peptide discovery, it is crucially important to be able to map the potential sites of cleavages of the proteases. This knowledge is used to later chemically modify the peptide drug to adapt it for the therapeutic use, making peptide stable against individual proteases or in complex medias. In some other cases it needed to make it specifically unstable for some proteases, as peptides could be used as a system to target delivery drugs on specific tissues or cells. The information about proteases, their sites of cleavages and substrates are widely spread across publications and collected in databases such as MEROPS. Therefore, it is possible to develop models to improve the understanding of the potential peptide drug proteolysis. We propose a new workflow to derive protease specificity rules and predict the potential scissile bonds in peptides for individual proteases. WebMetabase stores the information from experimental or external sources in a chemically aware database where each peptide and site of cleavage is represented as a sequence of structural blocks connected by amide bonds and characterized by its physicochemical properties described by Volsurf descriptors. Thus, this methodology could be applied in the case of non-standard amino acid. A frequency analysis can be performed in WebMetabase to discover the most frequent cleavage sites. These results were used to train several models using logistic regression, support vector machine and ensemble tree classifiers to map cleavage sites for several human proteases from four different families (serine, cysteine, aspartic and matrix metalloproteases). Finally, we compared the predictive performance of the developed models with other available public tools PROSPERous and SitePrediction.

Long-term adaptive evolution of genomically recodedEscherichia coli

Efforts are underway to construct several recoded genomes anticipated to exhibit multi-virus resistance, enhanced non-standard amino acid (NSAA) incorporation, and capability for synthetic biocontainment. Though we succeeded in pioneering the first genomically recoded organism (Escherichia colistrain C321.ΔA), its fitness is far lower than that of its non-recoded ancestor, particularly in defined media. This fitness deficit severely limits its utility for NSAA-linked applications requiring defined media such as live cell imaging, metabolic engineering, and industrial-scale protein production. Here, we report adaptive evolution of C321.ΔA for more than 1,000 generations in independent replicate populations grown in glucose minimal media. Evolved recoded populations significantly exceed the growth rates of both the ancestral C321.ΔA and non-recoded strains, permitting use of the recoded chassis in several new contexts. We use next-generation sequencing to identify genes mutated in multiple independent populations, and we reconstruct individual alleles in ancestral strains via multiplex automatable genome engineering (MAGE) to quantify their effects on fitness. Several selective mutations occur only in recoded evolved populations, some of which are associated with altering the translation apparatus in response to recoding, whereas others are not apparently associated with recoding, but instead correct for off-target mutations that occurred during initial genome engineering. This report demonstrates that laboratory evolution can be applied after engineering of recoded genomes to streamline fitness recovery compared to application of additional targeted engineering strategies that may introduce further unintended mutations. In doing so, we provide the most comprehensive insight to date into the physiology of the commonly used C321.ΔA strain.Significance StatementAfter demonstrating construction of an organism with an altered genetic code, we sought to evolve this organism for many generations to improve its fitness and learn what unique changes natural selection would bestow upon it. Although this organism initially had impaired fitness, we observed that adaptive laboratory evolution resulted in several selective mutations that corrected for insufficient translation termination and for unintended mutations that occurred when originally altering the genetic code. This work further bolsters our understanding of the pliability of the genetic code, it will help guide ongoing and future efforts seeking to recode genomes, and it results in a useful strain for non-standard amino acid incorporation in numerous contexts relevant for research and industry.

Engineering post-translational proofreading to discriminate non-standard amino acids

Progress in genetic code expansion requires accurate, selective, and high-throughput detection of non-standard amino acid (NSAA) incorporation into proteins. Here, we discover how the N-end rule pathway of protein degradation applies to commonly used NSAAs. We show that several NSAAs are N-end stabilizing and demonstrate that other NSAAs can be made stabilizing by rationally engineering the N-end rule adaptor protein ClpS. We use these insights to engineer a synthetic quality control method, termed “Post-Translational Proofreading” (PTP). By implementing PTP, false positive proteins resulting from misincorporation of structurally similar standard amino acids or undesired NSAAs rapidly degrade, enabling high-accuracy discrimination of desired NSAA incorporation. We illustrate the utility of PTP during evolution of the biphenylalanine orthogonal translation system used for synthetic biocontainment. Our new OTS is more selective and confers lower escape frequencies and greater fitness in all tested biocontained strains. Our approach presents a new paradigm for molecular recognition of amino acids in target proteins.

Changes in regional brain monoaminergic activity and temporary down-regulation in stress response from dietary supplementation with l-tryptophan in Atlantic cod (Gadus morhua)

The brain monoamines serotonin (5-hydroxytryptamine; 5-HT) and dopamine (DA) both play an integrative role in behavioural and neuroendocrine responses to challenges, and comparative models suggest common mechanisms for dietary modulation of transmission by these signal substances in vertebrates. Previous studies in teleosts demonstrate that 7 d of dietary administration with l-tryptophan (Trp), the direct precursor of 5-HT, suppresses the endocrine stress response. The present study investigated how long the suppressive effects of a Trp-enriched feed regimen, at doses corresponding to two, three or four times the Trp levels in commercial feed, last in juvenile Atlantic cod (Gadus morhua) when the fish are reintroduced to a diet with standard amino acid composition. We also wanted to determine whether Trp supplementation induced changes in brain monoaminergic neurochemistry in those forebrain structures innervated by DA- and 5-HTergic neurons, by measuring regional activity of DA and 5-HT in the lateral pallial regions (Dl) of the telencephalon and nucleus lateralis tuberis (NLT) of the hypothalamus. Dietary Trp resulted in a dose-dependent suppression in plasma cortisol among fish exposed to confinement stress on the first day following experimental diet; however, such an effect was not observed at 2 or 6 d after Trp treatment. Feeding the fish with moderate Trp doses also evoked a general increase in DA and 5-HT-ergic activity, suggesting that these neural circuits within the NLT and Dl may be indirectly involved in regulating the acute stress response.

Constructing a Syntheses Table of the Standard Amino Acid Based on the PAM250 Matrix

It is well known that there are some similarities among various naturally occurring amino acids. The standard amino acids have been grouped by their general properties and the chemical structures of their side chains. In this paper we divided the molecular weight of amino acid into two parts: backbone molecular weight Mband side chain molecular weight Ms. We naturally grouped the amino acids into two sets according to the rate of Ms/ Mb. We developed a method to construct a syntheses table to reflect the relevant physicochemical properties based on the PAM250 matrix and successfully established an elegant table of the twenty amino acids. Our work proved that PAM250 matrix could be used not only in finding reasonable alignments but also in grouping similar amino acid.