The 6th International Conference of D-Amino Acid Research (IDAR2024) and 18th Joint Conference of the D-Amino Acid Research Society Japan will be held at Kanazawa University in August 2024 between 21 (Wednesday) and 24 (Saturday). The website of IDAR2024 is open now, please visit the following:

Do you have news concerning the D-amino acids field to announce? Is there a relevant published paper to mention? Write us and take the advantage of this bimonthly Newsletter.





The Editor’s pick selection of the most intriguing papers is highlighted in yellow.


D-serine and D-amino acid oxidase levels in patients with schizophrenia spectrum disorders in the first episode and 6-month follow-up
Uzun Uysal E, Tomruk NB, Çakır Şen C, Yıldızhan E
J Psychiatr Res. 2024 May 3;175:123-130.
In this paper, the correlation between D-serine and D-amino acid oxidase (DAAO) levels were investigated in patients with first-episode schizophrenia spectrum disorders before treatment (89 patients) and after six months of treatment (41 patients). Before treatment, patients had significantly lower levels of D-serine, DAAO, and D-serine/DAAO ratio compared to 81 healthy individuals. The DAAO and D-serine levels of the patients were higher after six months of treatment. The DAAO levels correlated with antipsychotic dosage and with PANSS negative and total subscale scores, while no correlation was found with cognitive functions.


D-amino acids metabolism reflects the evolutionary origin of higher plants and their adaptation to the environment
Porras-Dominguez J., Lothier J., Limami A.M., Tcherkez G.
Plant Cell and Environment (2024), 47 (5), pp. 1503 – 1512. DOI: 10.1111/pce.14826
Over the past two decades, the occurrence of D-amino acids in plants has been reported and circumstantial evidence for a role in various processes, including interaction with soil microorganisms or interference with cellular signalling, has been provided. D-AAs can also be detrimental. Some inhibiting growth and development. Systemic analysis of sequences associated with D-AA metabolism enzymes shows that they are not simply inherited from cyanobacterial metabolism. Regardless of evolutionary steps, enzymes of D-AA metabolism, such as D-amino acid transferases or racemases, have been retained by higher plants and have not simply been eliminated, so it is likely that they fulfil important metabolic roles such as serine, folate or plastid peptidoglycan metabolism. The authors concluded that D-AA metabolism may have been critical to support metabolic functions required during the evolution of land plants.



In vivo labeling and intravital imaging of bacterial infection using a near-infrared fluorescent D-amino acid probe
Li Y, Zhou Y, Du Y, Gao P, Yang L, Wang W
Chembiochem. 2024 May 7:e202400283. doi: 10.1002/cbic.202400283. Online ahead of print.

This work reports on a near-infrared fluorescent D-amino acid (FDAA) probe, Cy7ADA, for in situ labeling and intravital imaging of bacterial infections in mice. The real-time visualization of the pathogens in a liver abscess model via intravital confocal microscopy is achieved, as well as the biodistributions.

Engineering a low-immunogenic mirror-image VHH against vascular endothelial growth factor

Aoki K, Higashi K, Oda S, Manabe A, Maeda K, Morise J, Oka S, Inuki S, Ohno H, Oishi S, Nonaka M ACS Chem Biol. 2024 May 17;19(5):1194-1205. doi: 10.1021/acschembio.4c00197
Immunogenicity is a major caveat of protein therapeutics, bringing to the generation of antidrug antibodies (ADAs). One promising solution to this issue is the use D-amino acids-containing proteins, which are resistant to proteolytic degradation in immune cells. The authors recently reported the chemical synthesis of the enantiomeric form of the variable domain of the antibody heavy chain (d-VHH) and here they developed a novel screening platform to identify a d-VHH specific for vascular endothelial growth factor A (VEGF-A). A d-VHH candidate that preferentially binds the native VEGF-A (l-VEGF-A) with submicromolar affinity was produced: this d-VHH elicited no ADAs, thus showing both reduced immunogenicity and improved efficacy.

Chemogenetic approaches to probe redox dysregulation in heart failure
Guo R, Spyropoulos F, Michel T
Free Radic Biol Med. 2024 May 1;217:173-178. doi: 10.1016/j.freeradbiomed.2024.03.027
Chemogenetics refers to experimental methods that use novel recombinant proteins that can be dynamically and uniquely regulated by specific biochemicals. Approaches based on yeast D-amino acid oxidase (DAAO) enable manipulation of intracellular redox metabolism through generation of hydrogen peroxide in the presence of D-amino acids: novel animal models allowed to characterize the impact of oxidative stress in heart failure and neurodegeneration. This review discusses chemogenetic approaches to manipulate oxidative stress in models of heart failure.

Colorimetric sensor array for the rapid distinction and detection of various antibiotic-resistant psychrophilic bacteria in raw milk based-on machine learning
Qin Y, Sun J, Huang W, Yue H, Meng F, Zhang M
Food Chem X. 2024 Mar 15;22:101281. doi: 10.1016/j.fochx.2024.101281
A rapid, inexpensive, and accurate colorimetric sensor for detecting psychrophilic bacteria was designed, comprising gold (Au) nanoparticles (NPs) modified by D-amino acids as color-metric probes. Based on the aggregation of Au NPs induced by psychrophilic bacteria, a noticeable color shift occurred within 6 h. Four primary psychrophilic bacteria in raw milk were successfully distinguished by learning the response patterns. Furthermore, a rapid colorimetric method was set up by combining Au/D-AA with antibiotics for the minimum inhibitory concentration of psychrophilic bacteria, which relied on differences in bacteria metabolic activity in response to diverse antibiotic treatments.

Microplate-based cryopreservation of adherent-cultured human cell lines using amino acids and proteins
Morita K, Yashiro T, Aoi T, Imamura R, Ohtake T, Yoshizaki N, Maruyama T
ACS Biomater Sci Eng. 2024 Apr 8;10(4):2442-2450. doi: 10.1021/acsbiomaterials.3c01834
Traditional cryoprotectants, e.g., dimethyl sulfoxide and glycerol, are effective in cryopreserving suspended cells, but they do not show sufficient efficacy for two-dimensional (2D)-cultured cells. Some L-amino acids have been reported to be natural and biocompatible cryoprotectants. Here, the cryoprotective effects of D- and L-amino acids and previously reported cryoprotectants were assessed using HepG2 cells cultured on a microplate without suspending the cells. D-Proline had the highest cryoprotective effect on 2D-cultured cells: it protects enzymes essential for cell survival from freeze-induced damage.


Immobilization of D-amino acid dehydrogenase from Ureibacillus thermosphaericus

Boros K., Gal L., Gal C.A., Wäscher M., Tomoiagă R.B., Toşa M.I., Pietruszka J., Bencze L.C. Process Biochemistry 2024 140, 45-55.

Immobilization of D-amino acid dehydrogenase from Ureibacillus thermosphaericus (UtDAADH) and its co-immobilization with the NADPH–regenerating glucose dehydrogenase (GDH) was studied. The best procedure was DAADH adsorbed onto the Purolite® resin: deMultifunctionality of arginine residues in the active sites of non-canonical D-amino acid transaminases
Bakunova AK, Matyuta IO, Minyaev ME, Isaikina TY, Boyko KM, Popov VO, Bezsudnova EY
Arch Biochem Biophys. 2024 Jun;756:110011. doi: 10.1016/
The role of arginine residues in the active site of pyridoxal-5′-phosphate (PLP)-dependent non-canonical D-amino acid transaminase from Haliscomenobacter hydrossis was investigated. The tandem of arginine residues R28 and R90, which form the conserved R-[RK] motif, not only facilitates effective substrate binding but also regulates the catalytic properties of PLP. Non-covalent interactions between residues R28, R90, and Y147 strengthen the hydrogen bond between Y147 and PLP, thereby maintaining the reactivity of the cofactor. Next, the R90 residue contributes to the stability of the holoenzyme. Finally, the R90I substitution induces structural changes yielding substrate promiscuity, as evidenced by the effective binding of substrates with and without the α-carboxylate group.

Experimental evidence of D-glutamate racemase activity in the uncultivated bacterium Candidatus Saccharimonas aalborgensis

Peñalver M, Paradela A, Palacios-Cuéllar C, Pucciarelli MG, García-Del Portillo F Environ Microbiol. 2024 Apr;26(4):e16621. doi: 10.1111/1462-2920.16621

The Candidate Phyla Radiation (CPR) encompasses widespread uncultivated bacteria with reduced genomes and limited metabolic capacities, such as the minimal set of enzymes required for peptidoglycan (PG) synthesis. Here, the distribution of D-amino acid racemases, as well as moonlighting enzymes that synthesize D-Glu or D-Ala, has been investigated. CPR bacteria do not exhibit these moonlighting activities and have, at most, one gene encoding either a Glu or Ala racemase. One of these ‘orphan’ racemases is a predicted Glu racemase (MurICPR) from the CPR bacterium Candidatus Saccharimonas aalborgenesis. This microorganism may couple Glu racemization to serine and D-Glu incorporation into the stem peptide.

Identification of a novel thermostable transaminase and its application in L-phosphinothricin biosynthesis
Liu H.-L., Yi P.-H., Wu J.-M., Cheng F., Liu Z.-Q., Jin L.-Q., Xue Y.-P., Zheng Y.-G.
Applied Microbiology and Biotechnology (2024), 108 (1), art. no. 184. DOI: 10.1007/s00253-024-13023-7
Transaminase (TA) is a crucial biocatalyst for enantioselective production of the herbicide L-phosphinothricin (L-PPT). The use of enzymatic cascades has been shown to effectively overcome the unfavorable thermodynamic equilibrium of TA-catalyzed transamination reaction, also increasing demand for TA stability. In this work, a novel thermostable transaminase from Pseudomonas thermotolerans (PtTA) was characterized and showed a high specific activity towards 2‐oxo‐4‐[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), with excellent thermostability and substrate tolerance. The enzyme was used in cascade systems for L-PPT biosynthesis. At 800 mM D,L-PPT, a 90.4% L-PPT yield was reached.


D-tryptophan, an eco-friendly natural, safe, and healthy compound with antimicrobial activity against food-borne pathogens: A systematic review
Moghimani M, Noori SMA, Afshari A, Hashemi M
Food Sci Nutr. 2024 Feb 1;12(5):3068-3079. doi: 10.1002/fsn3.3987. eCollection
D-amino acids are used as food preservatives. On this side, D-tryptophan in food reduces the requirement for high temperatures and their damaging effects on nutrients such as proteins and vitamins. This review reports about the antimicrobial effect of D-tryptophan on food-borne pathogens in vitro and in food models.

Efficient fermentative production of D-alanine and other D-amino acids by metabolically engineered Corynebacterium glutamicum
Tian S, Zhao G, Lv G, Wu C, Su R, Wang F, Wang Z, Liu Y, Chen N, Li Y
J Agric Food Chem. 2024 Apr 10;72(14):8039-8051. doi: 10.1021/acs.jafc.4c00914 Here, the authors observed that Corynebacterium glutamicum exhibits a remarkable tolerance to high concentrations of D-Ala, a crucial characteristic for establishing a successful fermentation process. By optimizing meso-diaminopilmelate dehydrogenases in different C. glutamicum strains and deleting L-Ala biosynthetic pathways, an efficient D-Ala fermentation system was generated. By fermentation in a 5-L bioreactor, a significant accumulation of L-Ala was obtained in the broth, which was subsequently diminished by adding an L-amino acid deaminase. The engineered strain DA-11 produced 85 g/L D-Ala with a yield of 0.30 g/g glucose, accompanied by an optical purity exceeding 99%. This fermentation platform has the potential to be extended for the synthesis of other D-AAs.


Enhancing the stability and therapeutic potential of the antimicrobial peptide Feleucin-K3 against multidrug-resistant A. baumannii through rational utilization of a D-amino acid substitution strategy
An Y, Guo X, Yan T, Jia Y, Jiao R, Cai X, Deng B, Bao G, Li Y, Yang W, Wang R, Sun W, Xie J
Biochem Pharmacol. 2024 May 7;225:116269. doi: 10.1016/j.bcp.2024.116269
Antimicrobial peptides (AMPs), which have a low probability of developing resistance, are promising antimicrobial agents for combating antibiotic resistance. Feleucin-K3 is an amphiphilic cationic AMP that exhibits broad-spectrum antimicrobial activity. In this paper, a series of Feleucin-K3 analogs containing hydrophobic D-amino acids were developed. The K-1dF, which replaced the phenylalanine of Feleucin-K3 with its enantiomer, exhibited potent antimicrobial activity with a therapeutic index of 46.97 and MICs between 4 to 8 μg/mL against both sensitive and multidrug-resistant Acinetobacter baumannii. K-1dF displayed a rapid bactericidal effect, a low propensity to develop resistance, and a synergistic effect when combined with antibiotics. Notably, it exhibited considerable or superior efficacy to imipenem against pneumonia and skin abscess infection.

Nontargeted identification of D-amino acid-containing peptides through enzymatic screening, chiral amino acid analysis, and LC-MS
Okyem S, Romanova EV, Tai HC, Checco JW, Sweedler JV
Methods Mol Biol. 2024;2758:227-240. doi: 10.1007/978-1-0716-3646-6_12
D-amino acid-containing peptides (DAACPs) in animals are a class of bioactive molecules formed via the posttranslational modification of peptides consisting of all-L-amino acids. This work describes a method for the identification of DAACPs that can be used to systematically survey peptides extracted from a tissue sample in a nontargeted manner.

A novel antimicrobial peptide with broad-spectrum and exceptional stability derived from the natural peptide Brevicidine
Yang P, Mao W, Zhang J, Yang Y, Zhang F, Ouyang X, Li B, Wu X, Ba Z, Ran K, Tian Y, Liu H, Zhang Y, Gou S, Zhong C, Ni J
Eur J Med Chem. 2024 Apr 5;269:116337. doi: 10.1016/j.ejmech.2024.116337
Brevicidine is a natural cyclic lipopeptide which exhibits remarkable antimicrobial activity against Gram-negative bacteria. Here, a comprehensive structure-activity relationship of Brevicidine was investigated through 20 newly synthesized cyclic lipopeptide analogs, resulting in the identification of an optimal linear analog 22 containing 5 D-amino acids and 4 non-natural amino acids. Compared to Brevicidine, analog 22 was easier to synthesize, and exerted broad spectrum antimicrobial activity and excellent stability. Furthermore, analog 22 demonstrated a rapid bactericidal effect by permeating non-specifically through the bacterial membranes, thereby minimizing the likelihood of inducing resistance, and exhibited remarkable efficacy in combating bacterial biofilms and reversing bacterial resistance to conventional antibiotics. It also effectively suppressed the growth of bacteria in vital organs of mice infected with S. aureus ATCC 25923.


A fast and efficient liquid chromatography-tandem mass spectrometry method for measuring L- and D-amino acids in the urine of patients with immunoglobulin A nephropathy
Zha Z, Wang R, Wang Q, Chen F, Ye Z, Li Y
Biomed Chromatogr. 2024 Jun;38(6):e5866. doi: 10.1002/bmc.5866
Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Recent evidence suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC-tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. A total of 14 D-amino acids and 20 L-amino acids were identified in the urine samples obtained from patients with IgAN and healthy individuals, showing significant variances in the concentrations of both enantiomers. The IgAN group exhibited lower
D-amino acids concentrations.

KCD: A prediction web server of knowledge-based circular dichroism

Jacinto-Méndez D, Granados-Ramírez CG, Carbajal-Tinoco MD Protein Sci. 2024 Apr;33(4):e4967. doi: 10.1002/pro.4967

A web server that predicts the far-UV circular dichroism (CD) spectra of proteins by utilizing their three-dimensional (3D) structures from the Protein Data Bank (PDB) is presented. The results of this knowledge-based CD method (KCD) are in good agreement with measured spectra that could include D-amino acids. The KCD method can be freely accessed from:


The D-amino acids International Research Center “DAAIR“ has been established in Gerenzano (Varese, Italy) in 2019 with the aim to support and perform scientific research projects and activities on the field of D-amino acids. The Center, located inside the Fondazione Istituto Insubrico Ricerca per la Vita, is aimed to represent a pole of excellence at international level for dissemination and research involving the D-amino acids (Director Silvia Sacchi).

The guiding principle is support the research projects aimed to investigate the involvement of D-amino acids in main physiological processes, from bacteria to humans. The ultimate goal is to actively participate to the elucidation of the mechanisms by which the D-amino acids perform specific functions, and to identify their presence and concentration in different organisms and compartments, also with regards to well-established functional states, with particular emphasis to pathological states. Understand the involvement of D-amino acids in important diseases as a way to set up novel therapeutic strategies.




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