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Advances in Research of D-Amino Acids
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Advances in Research of D-Amino Acids

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (15 August 2020) | Viewed by 30083

Special Issue Editor

Dr. Üner Kolukisaoglu

E-Mail Website
Guest Editor
Center for Molecular Biology of Plants (ZMBP), University of Tübingen, 72076 Tübingen, Germany
Interests: D-amino acids in plants

Special Issue Information

Dear Colleagues,

D-amino acids are found in all kingdoms of life like their chemical siblings, the proteinogenic L-amino acids. L-amino acids fulfill essential functions as building blocks of proteins and primary metabolites, but their enantiomers are found in other cellular contexts, which range from bacterial cell wall synthesis, to composition of antibiotics and neurotransmission, to plant nitrogen utilization and bacterial colonization of the soil. In the last decade, novel functions for D-amino acids have been found in different organisms, and many more are expected to be found in the future. In this Special Issue of IJMS, all aspects of D-amino acids from biosynthesis, metabolism, regulation, and transport to molecular and physiological functions will be focused on. Manuscripts such as short communications, original research papers, and reviews from researchers in this field are welcome to provide an overview of the newest findings and the future of D-amino acid research.

Dr. Üner Kolukisaoglu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • amino acid racemization
  • D-amino acid degradation
  • chiral amino acid analytics
  • microbial D-amino acid production
  • peptidoglycan
  • microbial biofilms
  • metabolism and physiological functions of D-amino acids in plants
  • D-amino acids in human health and disease

Published Papers (6 papers)

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Research

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13 pages, 3845 KiB  
Article
Serine Racemase Deletion Affects the Excitatory/Inhibitory Balance of the Hippocampal CA1 Network
by Eva Ploux, Valentine Bouet, Inna Radzishevsky, Herman Wolosker, Thomas Freret and Jean-Marie Billard
Int. J. Mol. Sci. 2020, 21(24), 9447; https://doi.org/10.3390/ijms21249447 - 11 Dec 2020
Cited by 10 | Viewed by 2202
Abstract
d-serine is the major co-agonist of N-methyl-D-aspartate receptors (NMDAR) at CA3/CA1 hippocampal synapses, the activation of which drives long-term potentiation (LTP). The use of mice with targeted deletion of the serine racemase (SR) enzyme has been an important tool to uncover the [...] Read more.
d-serine is the major co-agonist of N-methyl-D-aspartate receptors (NMDAR) at CA3/CA1 hippocampal synapses, the activation of which drives long-term potentiation (LTP). The use of mice with targeted deletion of the serine racemase (SR) enzyme has been an important tool to uncover the physiological and pathological roles of D-serine. To date, some uncertainties remain regarding the direction of LTP changes in SR-knockout (SR-KO) mice, possibly reflecting differences in inhibitory GABAergic tone in the experimental paradigms used in the different studies. On the one hand, our extracellular recordings in hippocampal slices show that neither isolated NMDAR synaptic potentials nor LTP were altered in SR-KO mice. This was associated with a compensatory increase in hippocampal levels of glycine, another physiologic NMDAR co-agonist. SR-KO mice displayed no deficits in spatial learning, reference memory and cognitive flexibility. On the other hand, SR-KO mice showed a weaker LTP and a lower increase in NMDAR potentials compared to controls when GABAA receptors were pharmacologically blocked. Our results indicate that depletion of endogenous D-serine caused a reduced inhibitory activity in CA1 hippocampal networks, altering the excitatory/inhibitory balance, which contributes to preserve functional plasticity at synapses and to maintain related cognitive abilities. Full article
(This article belongs to the Special Issue Advances in Research of D-Amino Acids)
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Review

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18 pages, 965 KiB  
Review
New Evidence on the Role of D-Aspartate Metabolism in Regulating Brain and Endocrine System Physiology: From Preclinical Observations to Clinical Applications
by Alessandro Usiello, Maria Maddalena Di Fiore, Arianna De Rosa, Sara Falvo, Francesco Errico, Alessandra Santillo, Tommaso Nuzzo and Gabriella Chieffi Baccari
Int. J. Mol. Sci. 2020, 21(22), 8718; https://doi.org/10.3390/ijms21228718 - 18 Nov 2020
Cited by 19 | Viewed by 5524
Abstract
The endogenous amino acids serine and aspartate occur at high concentrations in free D-form in mammalian organs, including the central nervous system and endocrine glands. D-serine (D-Ser) is largely localized in the forebrain structures throughout pre and postnatal life. Pharmacologically, D-Ser plays a [...] Read more.
The endogenous amino acids serine and aspartate occur at high concentrations in free D-form in mammalian organs, including the central nervous system and endocrine glands. D-serine (D-Ser) is largely localized in the forebrain structures throughout pre and postnatal life. Pharmacologically, D-Ser plays a functional role by acting as an endogenous coagonist at N-methyl-D-aspartate receptors (NMDARs). Less is known about the role of free D-aspartate (D-Asp) in mammals. Notably, D-Asp has a specific temporal pattern of occurrence. In fact, free D-Asp is abundant during prenatal life and decreases greatly after birth in concomitance with the postnatal onset of D-Asp oxidase expression, which is the only enzyme known to control endogenous levels of this molecule. Conversely, in the endocrine system, D-Asp concentrations enhance after birth during its functional development, thereby suggesting an involvement of the amino acid in the regulation of hormone biosynthesis. The substantial binding affinity for the NMDAR glutamate site has led us to investigate the in vivo implications of D-Asp on NMDAR-mediated responses. Herein we review the physiological function of free D-Asp and of its metabolizing enzyme in regulating the functions of the brain and of the neuroendocrine system based on recent genetic and pharmacological human and animal studies. Full article
(This article belongs to the Special Issue Advances in Research of D-Amino Acids)
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19 pages, 580 KiB  
Review
Advances in D-Amino Acids in Neurological Research
by James M. Seckler and Stephen J. Lewis
Int. J. Mol. Sci. 2020, 21(19), 7325; https://doi.org/10.3390/ijms21197325 - 3 Oct 2020
Cited by 32 | Viewed by 6103
Abstract
D-amino acids have been known to exist in the human brain for nearly 40 years, and they continue to be a field of active study to today. This review article aims to give a concise overview of the recent advances in D-amino acid [...] Read more.
D-amino acids have been known to exist in the human brain for nearly 40 years, and they continue to be a field of active study to today. This review article aims to give a concise overview of the recent advances in D-amino acid research as they relate to the brain and neurological disorders. This work has largely been focused on modulation of the N-methyl-D-aspartate (NMDA) receptor and its relationship to Alzheimer’s disease and Schizophrenia, but there has been a wealth of novel research which has elucidated a novel role for several D-amino acids in altering brain chemistry in a neuroprotective manner. D-amino acids which have no currently known activity in the brain but which have active derivatives will also be reviewed. Full article
(This article belongs to the Special Issue Advances in Research of D-Amino Acids)
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13 pages, 1164 KiB  
Review
d-Amino Acids in Plants: Sources, Metabolism, and Functions
by Üner Kolukisaoglu
Int. J. Mol. Sci. 2020, 21(15), 5421; https://doi.org/10.3390/ijms21155421 - 30 Jul 2020
Cited by 20 | Viewed by 4766
Abstract
Although plants are permanently exposed to d-amino acids (d-AAs) in the rhizosphere, these compounds were for a long time regarded as generally detrimental, due to their inhibitory effects on plant growth. Recent studies showed that this statement needs a critical [...] Read more.
Although plants are permanently exposed to d-amino acids (d-AAs) in the rhizosphere, these compounds were for a long time regarded as generally detrimental, due to their inhibitory effects on plant growth. Recent studies showed that this statement needs a critical revision. There were several reports of active uptake by and transport of d-AAs in plants, leading to the question whether these processes happened just as side reactions or even on purpose. The identification and characterization of various transporter proteins and enzymes in plants with considerable affinities or specificities for d-AAs also pointed in the direction of their targeted uptake and utilization. This attracted more interest, as d-AAs were shown to be involved in different physiological processes in plants. Especially, the recent characterization of d-AA stimulated ethylene production in Arabidopsis thaliana revealed for the first time a physiological function for a specific d-AA and its metabolizing enzyme in plants. This finding opened the question regarding the physiological or developmental contexts in which d-AA stimulated ethylene synthesis are involved in. This question and the ones about the transport characteristics of d-AAs, their metabolism, and their different physiological effects, are the focus of this review. Full article
(This article belongs to the Special Issue Advances in Research of D-Amino Acids)
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17 pages, 1638 KiB  
Review
Biosensors for D-Amino Acids: Detection Methods and Applications
by Elena Rosini, Paola D’Antona and Loredano Pollegioni
Int. J. Mol. Sci. 2020, 21(13), 4574; https://doi.org/10.3390/ijms21134574 - 27 Jun 2020
Cited by 27 | Viewed by 4342
Abstract
D-enantiomers of amino acids (D-AAs) are only present in low amounts in nature, frequently at trace levels, and for this reason, their biological function was undervalued for a long time. In the past 25 years, the improvements in analytical methods, such as gas [...] Read more.
D-enantiomers of amino acids (D-AAs) are only present in low amounts in nature, frequently at trace levels, and for this reason, their biological function was undervalued for a long time. In the past 25 years, the improvements in analytical methods, such as gas chromatography, HPLC, and capillary electrophoresis, allowed to detect D-AAs in foodstuffs and biological samples and to attribute them specific biological functions in mammals. These methods are time-consuming, expensive, and not suitable for online application; however, life science investigations and industrial applications require rapid and selective determination of D-AAs, as only biosensors can offer. In the present review, we provide a status update concerning biosensors for detecting and quantifying D-AAs and their applications for safety and quality of foods, human health, and neurological research. The review reports the main challenges in the field, such as selectivity, in order to distinguish the different D-AAs present in a solution, the simultaneous assay of both L- and D-AAs, the production of implantable devices, and surface-scanning biosensors. These innovative tools will push future research aimed at investigating the neurological role of D-AAs, a vibrant field that is growing at an accelerating pace. Full article
(This article belongs to the Special Issue Advances in Research of D-Amino Acids)
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16 pages, 17900 KiB  
Review
Advances in Enzymatic Synthesis of D-Amino Acids
by Loredano Pollegioni, Elena Rosini and Gianluca Molla
Int. J. Mol. Sci. 2020, 21(9), 3206; https://doi.org/10.3390/ijms21093206 - 1 May 2020
Cited by 27 | Viewed by 6516
Abstract
In nature, the D-enantiomers of amino acids (D-AAs) are not used for protein synthesis and during evolution acquired specific and relevant physiological functions in different organisms. This is the reason for the surge in interest and investigations on these “unnatural” molecules observed in [...] Read more.
In nature, the D-enantiomers of amino acids (D-AAs) are not used for protein synthesis and during evolution acquired specific and relevant physiological functions in different organisms. This is the reason for the surge in interest and investigations on these “unnatural” molecules observed in recent years. D-AAs are increasingly used as building blocks to produce pharmaceuticals and fine chemicals. In past years, a number of methods have been devised to produce D-AAs based on enantioselective enzymes. With the aim to increase the D-AA derivatives generated, to improve the intrinsic atomic economy and cost-effectiveness, and to generate processes at low environmental impact, recent studies focused on identification, engineering and application of enzymes in novel biocatalytic processes. The aim of this review is to report the advances in synthesis of D-AAs gathered in the past few years based on five main classes of enzymes. These enzymes have been combined and thus applied to multi-enzymatic processes representing in vitro pathways of alternative/exchangeable enzymes that allow the generation of an artificial metabolism for D-AAs synthetic purposes. Full article
(This article belongs to the Special Issue Advances in Research of D-Amino Acids)
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