Amino Derivatives Research Articles

Integrative Physiological, Transcriptional, and Metabolic Analyses Provide Insights Into Response Mechanisms of Prunus persica to Autotoxicity Stress.

Autotoxicity is known as a critical factor in replanting problem that reduces land utilization and creates economic losses. Benzoic acid (BA) is identified as a major autotoxin in peach replant problem, and causes stunted seedling growth or even death. However, the physiological and molecular mechanisms of peach response to BA stress remain elusive. Here, we comprehensively studied the morphophysiological, transcriptional, and metabolic responses of peach plants to BA toxicity. Results showed that BA stress inhibited peach seedlings growth, decreased chlorophyll contents and fluorescence levels, as well as disturbed mineral metabolism. The contents of hydrogen peroxide, superoxide anion, and malondialdehyde, as well as the total antioxidant capacity, were significantly increased under BA stress. A total of 6,319 differentially expressed genes (DEGs) were identified after BA stress, of which the DEGs related to photosynthesis, redox, and ion metabolism were greatly changed; meanwhile, numerous stress-responsive genes (HSPs, GSTs, GR, and ABC transporters) and transcription factors (MYB, AP2/ERF, NAC, bHLH, and WRKY) were noticeably altered under BA stress. BA induced metabolic reprogramming, and 74 differentially accumulated metabolites, including amino acids and derivatives, fatty acids, organic acids, sugars, and sugar alcohols, were identified in BA-stressed roots. Furthermore, an integrated analysis of genes and metabolites indicated that most of the co-mapped KEGG pathways were enriched in amino acid and carbohydrate metabolism, which implied a disturbed carbon and nitrogen metabolism after BA stress. The findings would be insightful in elucidating the mechanisms of plant response to autotoxicity stress, and help guide crops in alleviating replant problem.

Biocidal properties investigation of the new guanidine-containing alkoxysilanes and siloxanes and epoxy materials modified by them

This article presents a synthesis of stable guanidine-containing alkoxysilyl derivatives based on the synthesis procedure through amino derivatives and ylide of thiourea suggested previously. Amino- and mercapto-containing siloxane oligomers were synthesized by hydrolytic co-condensation based on the silanes thus obtained, and the biocidal activity of their aqueous solutions in comparison with the starting monomers was studied. The prospects of using the resulting compounds as biocidal additives to epoxy compositions and a high biocidal activity at their small concentrations in the cured material against S. aureus, E. coli, and C. albicans strains were demonstrated.

PdII on Guanidine-Functionalized Fe3O4 Nanoparticles as an Efficient Heterogeneous Catalyst for Suzuki-Miyaura Cross-Coupling and Reduction of Nitroarenes in Aqueous Media.

This paper presents guanidine-functionalized Fe3O4 magnetic nanoparticle-supported palladium (II) (Fe3O4@Guanidine-Pd) as an effective catalyst for Suzuki–Miyaura cross-coupling of aryl halides using phenylboronic acids and also for selective reduction of nitroarenes to their corresponding amines. Fe3O4@Guanidine-Pd synthesized is well characterized using FT-IR spectroscopy, XRD, SEM, TEM, EDX, thermal gravimetric analysis, XPS, inductively coupled plasma-optical emission spectroscopy, and vibrating sample magnetometry analysis. The prepared Fe3O4@Guanidine-Pd showed effective catalytic performance in the Suzuki–Miyaura coupling reactions by converting aryl halides to their corresponding biaryl derivatives in an aqueous environment in a shorter reaction time and with a meagerly small amount of catalyst (0.22 mol %). Also, the prepared Fe3O4@Guanidine-Pd effectively reduced nitroarenes to their corresponding amino derivatives in aqueous media at room temperature with a high turnover number and turnover frequency with the least amount of catalyst (0.13 mol %). The most prominent feature of Fe3O4@Guanidine-Pd as a catalyst is the ease of separation of the catalyst from the reaction mixture after the reaction with the help of an external magnet with good recovery yield and also reuse of the recovered catalyst for a few cycles without significant loss in its catalytic activity.

Pyrrolotriazinone as an Underexplored Scaffold in Drug Discovery.

Heterocyclic amino derivatives have been extensively synthesized and validated as potent bioactive compounds, and nowadays, numerous marketed drugs share these scaffolds, from very simple structures (monoamino, monocyclic compounds) to much more complex molecules (polycyclic derivatives with two or more nitrogen atoms within the (fused) rings). In a constant quest for new chemical entities in drug discovery, a few novel heterocycles have emerged in recent years as promising building blocks for the obtainment of bioactive modulators. In this context, pyrrolotriazinones have attracted attention, and some show promising biological activities. Here, we offer an extensive review of pyrrolo[2,1-f][1,2,4]triazin-4(1H)-one and pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one, describing their biological properties en route to drug discovery.

Synthesis and in vitro antifungal activity of new Michael-type amino derivatives of xanthatin, a natural sesquiterpene lactone from Xanthium strumarium L.

Structural optimization using plant secondary metabolites as templates is one of the important approach to discover pesticide molecules with novel skeletons. Xanthatin, a natural sesquiterpene lactone isolated from the Xanthium plants (Family: Compositae), exhibits important biological properties. In this work, a series of Michael-type amino derivatives were prepared from xanthatin and their structures were characterized by 1H NMR, 13C NMR and HR-MS, and their antifungal activities against several phytopathogenic fungi were evaluated according to the spore germination method and mycelium growth rate method in vitro. The results illustrated that compounds 2g (IC50 = 78.91 µg/mL) and 2o (IC50 = 64.51 µg/mL) exhibited more promising inhibition activity against spores of F. solani than precursor xanthatin, compounds 2g, 2l, and 2r exhibited remarkable antifungal effect on C. mandshurica with the average inhibition rates (AIRs) >90%, whereas the AIR of xanthatin was only 59.34%. Meanwhile, the preliminary structure–activity relationships suggested that the amino containing 2-methoxyethyl or 4-chlorophenylmethyl group appended in the C-13 position of xanthatin could yield potential compounds against fungal spores, and the exocyclic double bond of xanthatin is essential to maintain its mycelial growth inhibitory activity. Therefore, the aforementioned findings indicate that partial xanthatin amino-derivatives could be considered for further exploration as the potential lead structures toward development of the new environmentally friendly fungicidal candidates for sustainable crop protection.

Enhanced Cr(VI) sorption capacity of the mechanochemically synthesized defective UiO-66 and UiO-66-NH2

Sorption of hexavalent chromium has become a growing global concern due to its high aqueous solubility and good mobility in underground environments. Among other Metal-Organic Frameworks (MOFs), water-stable Zr-MOFs have been recently investigated for the efficient decontamination of aqueous solution from Cr(VI). Herein, Zr-benzene dicarboxylate (UiO-66) and its amino derivative, Zr-NH2-benzene dicarboxylate (UiO-66-NH2), were prepared via a facile, benign mechanochemical method (Liquid Assisted Grinding, LAG) and for the first time applied to sorption studies for Cr(VI) removal. Through the comparative examination of the mechanochemically isolated UiO-66 (LAG) and UiO-66-NH2 (LAG) with the same Zr-MOFs made via conventional solvothermal synthesis (solvothermal, SOL) UiO-66 (SOL) and UiO-66-NH2 (SOL), we demonstrate better performance of the former towards Cr(VI) sorption. The Cr(VI) sorption kinetics for all compounds were well described by the pseudo second-order kinetic model, while the calculated sorption capacities of UiO-66 (LAG) and UiO-66-NH2 (LAG) for Cr(VI) (at pH 3) by the Langmuir model were 28.8 and 36.6 mg/g, respectively, overperforming those of UiO-66 (SOL) and UiO-66-NH2 (SOL), which were found to be 24.9 mg/g and 26.1 mg/g, respectively. Our findings point out that the increased missing-linker defects, generated through milling, boost Cr(VI) sorption. In addition, this work opens the perspective for the implementation of mechanochemical synthesis in order to examine the performance of other known MOF sorbents towards water remediation applications.

Chemical and bacterial composition of Broussonetia papyrifera leaves ensiled at two ensiling densities with or without Lactobacillus plantarum

Paper mulberry (Broussonetia papyrifera) is an important crop that can be used for the production of paper and animal feed. The aim of this study was to study the influence of ensiling density (250 and 500 kg/m3) and a lactic acid bacteria inoculant on fermentation parameters, bacterial communities and metabolites of B. papyrifera leaves silage. Silages ensiled at 500 kg/m3 showed lower (P < 0.05) pH and coliform bacteria number than 250 kg/m3. LP increased (P < 0.05) the content of lactic acid and decreased (P < 0.05) the pH value, the contents of ammonia-N and butyric acid, and the number of coliform bacteria. Higher abundance of Enterococcus and Lactococcus were observed in B. papyrifera leaves ensiled at 500 kg/m3 than 250 kg/m3 and Lactobacillus dominated in all LP treated silages. LP reduced the abundance of Clostridium and Enterobacter. 834 chemicals were identified in B. papyrifera leaves silage, including 155 lipids, 145 phenolic acids, 117 flavonoids, 94 amino acids and derivatives, 80 organic acids, 69 alkaloids, 56 nucleotides and derivatives, 18 lignans and coumarins, 13 terpenoids, 11tannins. 213 differentially accumulated metabolites were identified when compared 250 kg/m3 to 500 kg/m3, while only 23 were detected after LP was added. These metabolites were correlated with bacterial community, especially Sphingomonas and Lactobacillus. In conclusions, ensiling density influenced bacterial communities and metabolites of the silage. Lactic acid bacteria inoculants application is a feasible way to obtain well fermented B. papyrifera leaves silage even ensiled at a relative low ensiling density. It provides insight into the metabolites, bacterial community and their relationship in B. papyrifera leaves silage. Furthermore, it might be helpful for high quality silage production when compacting machine is lacking.

A base-controlled switch of SO2 reincorporation in photocatalyzed radical difunctionalization of alkenes

A base-controlled switch of SO2 reincorporation in photocatalyzed radical difunctionalization of alkenes

Analysis of metabolite differences in skin between Clapp's Favorite and its mutant Red Clapp's Favorite through non-targeted metabolomics

为了探究西洋梨品种茄梨及其红色芽变红茄梨成熟期果皮代谢产物差异,采用超高效液相色谱-质谱联用技术,对茄梨和红茄梨成熟期果皮进行非靶向代谢组学研究。通过主成分分析和正交偏最小二乘判别分析,构建了多变量统计分析模型,结合模型和变量重要性投影与最大差异倍数值,基于精确质量数、二级碎片以及同位素分布,使用PMDB(Plant Metabolome Database)数据库进行定性,筛选并鉴定出茄梨和红茄梨果皮中显著性变化(P<0.05, VIP(variable importance in project)≥1)的差异代谢物有83种,主要包括酚酸类、黄酮类和氨基酸类物质,涉及类黄酮代谢、氨基酸代谢、苯丙烷类代谢等代谢途径,其中53种物质含量上调,30种物质表达下调。通过KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库进一步对差异代谢物质进行通路富集分析,差异代谢物主要分布在20条代谢途径中,P<0.05的代谢途径有6条,分别是类黄酮生物合成、黄酮和黄酮醇生物合成、苯丙烷生物合成、丁酸酯代谢、苯丙氨酸代谢、酪氨酸代谢。这些差异代谢物的变化可能是导致茄梨和红茄梨果皮色泽不同的原因。该研究从植物代谢组学角度初步揭示了茄梨和红茄梨成熟期果皮的代谢产物差异性。

Adsorption of Phenol by Nitro and Amino Derivatives of Petroleum Asphaltenes

Adsorption of Phenol by Nitro and Amino Derivatives of Petroleum Asphaltenes

In silico and multi-spectroscopic analyses on the interaction of 5-amino-8-hydroxyquinoline and bovine serum albumin as a potential anticancer agent

5-Amino-8-hydroxyquinoline (5A8HQ), an amino derivative of 8-hydroxyquinoline, has become a potential anticancer candidate because of its promising proteasome inhibitory activity to overcome and yet synergize bortezomib for fighting cancers. Therefore, in this study, its physicochemical properties and interaction activities with serum protein have extensively been elucidated by both in vitro and in silico approaches to fulfill the pharmacokinetic and pharmacodynamic gaps. 5A8HQ exhibited the drug-likeness properties, where oral administration seems to be a route of choice owing to its high-water solubility and intestinal absorptivity. Multi-spectroscopic investigations suggested that 5A8HQ tended to associate with bovine serum albumin (BSA), a representative of serum protein, via the ground-state complexation. It apparently bound in a protein cleft between subdomains IIA and IIIA of BSA as suggested by the molecular docking and molecular dynamics simulations. The binding was mainly driven by hydrogen bonding and electrostatic interactions with a moderate binding constant at 104 M−1, conforming with the predicted free fraction in serum at 0.484. Therefore, 5A8HQ seems to display a good bioavailability in plasma to reach target sites and exerts its potent pharmacological activity. Likewise, serum albumin is a good candidate to be reservoir and transporter of 5A8HQ in the circulatory system.

Impact of the Pd2Spm (Spermine) Complex on the Metabolism of Triple-Negative Breast Cancer Tumors of a Xenograft Mouse Model.

The interest in palladium(II) compounds as potential new anticancer drugs has increased in recent years, due to their high toxicity and acquired resistance to platinum(II)-derived agents, namely cisplatin. In fact, palladium complexes with biogenic polyamines (e.g., spermine, Pd2Spm) have been known to display favorable antineoplastic properties against distinct human breast cancer cell lines. This study describes the in vivo response of triple-negative breast cancer (TNBC) tumors to the Pd2Spm complex or to cisplatin (reference drug), compared to tumors in vehicle-treated mice. Both polar and lipophilic extracts of tumors, excised from a MDA-MB-231 cell-derived xenograft mouse model, were characterized through nuclear magnetic resonance (NMR) metabolomics. Interestingly, the results show that polar and lipophilic metabolomes clearly exhibit distinct responses for each drug, with polar metabolites showing a stronger impact of the Pd(II)-complex compared to cisplatin, whereas neither drug was observed to significantly affect tumor lipophilic metabolism. Compared to cisplatin, exposure to Pd2Spm triggered a higher number of, and more marked, variations in some amino acids, nucleotides and derivatives, membrane precursors (choline and phosphoethanolamine), dimethylamine, fumarate and guanidine acetate, a signature that may be relatable to the cytotoxicity and/or mechanism of action of the palladium complex. Putative explanatory biochemical hypotheses are advanced on the role of the new Pd2Spm complex in TNBC metabolism.

Insights into Paraben Adsorption by Metal-Organic Frameworks for Analytical Applications.

Metal-organic frameworks (MOFs) are attractive materials used as sorbents in analytical microextraction applications for contaminants of emerging concern (CECs) from environmental liquid matrices. The demanding specs for a sorbent in the analytical application can be comprehensively studied by considering the interactions of the target analytes with the frameworks by the use of single-crystal X-ray diffraction, computational analysis, and adsorption studies, including the kinetic ones. The current study intends a better understanding of the interactions of target CECs (particularly, propylparaben (PPB) as a model) and three Zn-based layered pillared MOFs: CIM-81 [Zn2(tz)2(bdc)] (Htz = 1,2,4-triazole and H2bdc = 1,4-benzenedicarboxylic acid) and their amino derivatives [Zn2(NH2-tz)2(bdc)] CIM-82 and [Zn2(tz)2(NH2-bdc)] CIM-83 (NH2-Htz = 3-amino-1,2,4-triazole and NH2-H2bdc = 2-amino-1,4-benzenedicarboxylic acid). The crystal structures of the two solvate compounds (dma@CIM-81 (dma = dimethylacetamide) and acetone@CIM-81) were solved by single-crystal X-ray diffraction to determine the points of interaction between the framework and the guest molecules. They also served as a starting point for the computational modeling of the PPB@CIM-81 compound, showing that up to two PPB molecules can be hosted in one of the pores, while only one can be trapped in the second pore type, leading to a maximum theoretical capacity of 291.9 mg g-1. This value is close to the value obtained by the adsorption isotherm experiment for CIM-81 (283 mg g-1). This value is, by far, higher than those previously reported for other materials for the removal of PPB from water, and also higher than the experimental values obtained for CIM-82 (54 mg g-1) and CIM-83 (153 mg g-1). The kinetics of adsorption is not very fast, with uptake of about 40% in 3 h, although a 70% release in methanol is achieved in 1 h. In addition, a further comparison of performance in analytical microextraction (requiring only 10 mg of CIM-81) was carried out together with chromatographic analysis to support all insights attained, with the method being able to monitor CECs as low as μg L-1 levels in complex environmental water samples, thus performing successfully for water monitoring even in multicomponent scenarios.

Investigation and dynamic profiling of oligopeptides, free amino acids and derivatives during Pu-erh tea fermentation by ultra-high performance liquid chromatography tandem mass spectrometry

Microbial fermentation is the critical step of Pu-erh tea manufacture, which will induce dramatic changes in the chemical composition and content of tea. In this research, we applied multi-methods based on UHPLC-Q-TOF/MS to profile the dynamic changes of oligopeptides, free amino acids, and derivatives (OPADs) during Pu-erh fermentation and predicted the potential bioactivities in silico. A total of 60 oligopeptides, 18 free amino acids, and 42 amino acid derivatives were identified, and the contents of most of them decreased after fermentation. But several N-acetyl amino acids increased 7–36 times after fermentation, and they might be the potential inhibitors of neurokinin-1 receptor. Moreover, the results of metamicrobiology showed Aspergillus niger and Aspergillus luchuensis were more prominent to metabolize protein, oligopeptides, and amino acids. Overall, these findings provide valuable insights about dynamic variations of OPADs during Pu-erh tea fermentation and are beneficial for guiding practical fermentation and quality control of Pu-erh tea.

The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study.

Herein, we report on the reaction of nitro-substituted azidobenzofuroxans with 1,3-dicarbonyl compounds in basic media. The known reactions of benzofuroxans and azidofuroxans with 1,3-dicarbonyl compounds in the presence of bases are the 1,3-dipolar cycloaddition and the Beirut reaction. In contrast with this, azidonitrobenzofuroxan reacts with 1,3-carbonyl compounds through Regitz diazo transfer, which is the first example of this type of reaction for furoxan derivatives. This difference is seemingly due to the strong electron-withdrawing effect of the superelectrophilic azidonitrobenzofuroxan, which serves as the azido transfer agent rather than 1,3-dipole in this case.

SLC36 family of proton-coupled amino acid transporters in GtoPdb v.2021.3

Members of the SLC36 family of proton-coupled amino acid transporters are involved in membrane transport of amino acids and derivatives. The four transporters show variable tissue expression patterns and are expressed in various cell types at the plasma-membrane and in intracellular organelles. PAT1 is expressed at the luminal surface of the small intestine and absorbs amino acids and derivatives [3]. In lysosomes, PAT1 functions as an efflux mechanism for amino acids produced during intralysosomal proteolysis [2, 18]. PAT2 is expressed at the apical membrane of the renal proximal tubule [6] and at the plasma-membrane in brown/beige adipocytes [20]. PAT1 and PAT4 are involved in regulation of the mTORC1 pathway [11]. More comprehensive lists of substrates can be found within the reviews under Further Reading and in the references [3].

Synthesis of 1,8‐Cineole Derivatives from 3‐Carene

AbstractWith the purpose of developing high‐value utilization approach for 3‐carene, various 1,8‐cineole derivatives bearing Br, OH, and NH2 groups at C‐6 were synthesized starting from it, following a new method of synthesis. The structure of 1,8‐cineole was established from the structure of carene by first introducing an OH and then carrying out ring‐opening and nucleophilic substitution reactions under acidic conditions. Br was simultaneously introduced at C‐6 as an active reaction site. The acidity of the medium significantly influenced the efficiency of the reaction. It was observed that trimethylsilyl bromide was the ideal reagent to carry out the reaction. 6‐Bromo‐1,8‐cineole was prepared from 3‐carene via a two‐steps process at 20 °C. The reaction time was ≤3 h. The maximum extent of conversion was 98.58 % and a selectivity of 60.66 % was achieved. Then, we synthesized two other compounds with high reactivities from 6‐bromo‐1,8‐cineole. 6‐Hydroxyl‐1,8‐cineole was synthesized by reacting 6‐bromo‐1,8‐cineole with H2O at 65 °C for 1 h. The extent of conversion was 98.49 % and the selectivity was 87.86 %. A hydroxyl derivative with &gt;90 % purity was obtained after removing the solvent. 6‐Amino‐1,8‐cineole together with 6‐hydroxyl‐1,8‐cineole were synthesized by reacting 6‐bromo‐1,8‐cineole with ammonia with the conversion was &gt;98 % under 70 °C for 1 h. Lower feed ratio of ammonia to 6‐bromo‐1,8‐cineole was good for the yield of amino derivative. The hydroxyl/amino ratio decreased from 4.0 to 1.6 with the feed ratio decreased from 8 to 4. The hydroxyl derivative and amino derivative could be efficiently separated by adjusting the pH of the reaction medium to obtain an amino derivative (&gt;93 % purity).

2D Strategy for the Construction of an Enzyme-Activated NIR Fluorophore Suitable for the Visual Sensing and Profiling of Homologous Nitroreductases from Various Bacterial Species.

Nitroreductases (NTRs) mediate the reduction of nitroaromatic compounds to the corresponding nitrite, hydroxylamine, or amino derivatives. The activity of NTRs in bacteria facilitates the metabolic activation and antibacterial activity of 5-nitroimidazoles. Therefore, NTR activity correlates with the drug susceptibility and resistance of pathogenic bacteria. As such, it is important to develop a rapid and visual assay for the real-time sensing of bacterial NTRs for the evaluation and development of antibiotics. Herein, an activatable near-infrared fluorescent probe (HC–NO2) derived from a hemicyanine fluorophore was designed and developed based on two evaluation factors, including the calculated partition coefficient (Clog P) and fluorescence wavelength. Using HC–NO2 as the special substrate of NTRs, NTR activity can be assayed efficiently, and then, bacteria can be imaged based on the detection of NTRs. More importantly, a sensitive in-gel assay using HC–NO2 has been developed to selectively identify NTRs and sensitively determine NTR activity. Using the in-gel assay, NTRs from various bacterial species have been profiled visually from the “fluorescence fingerprints”, which facilitates the rapid identification of NTRs from bacterial lysates. Thus, various homologous NTRs were identified from three metronidazole-susceptible bacterial species as well as seven unsusceptible species, which were confirmed by the whole-genome sequence. As such, the evaluation of NTRs from different bacterial species should help improve the rational usage of 5-nitroimidazole drugs as antibiotics.

Metabolite analysis in Nymphaea ‘Blue Bird’ petals reveal the roles of flavonoids in color formation, stress amelioration, and bee orientation

In this study, metabolome of open petals (OP) and closed petals (CP) from Nymphaea ‘Blue Bird’ was firstly investigated. A total of 455 metabolites was identified in Nymphaea ‘Blue Bird’ petals, which was mainly composed of 100 flavonoids, 83 phenolic acids, 64 amino acids and derivatives, 60 lipids, 32 alkaloids, 32 organic acids, 24 nucleotides and derivatives, and 12 lignans and coumarins. By differential analysis, 192 metabolites were identified with variable importance in project ≥ 1, among which 83 and 109 metabolites were up- and down-regulated in OP group, respectively. Further analysis (Log2 fold change ≥ 1) identified 26 and 7 metabolites exhibited significantly lower and higher contents in CP group, relative to OP group. Importantly, KEGG analysis indicated that flavonoid biosynthesis exhibited the most significant enrichment. qRT-PCR analysis indicated that the PAL, CHS, and HCDBR genes showed a significantly higher expression in OP group than in CP group. These data explain the increase of naringenin chalcone and phloretin in OP. However, there was no significant difference of total flavonoids between OP and CP groups. Considering the increase of H2O2 content and ultraviolet (UV) absorption peak in OP, our results implied that diurnal stressful conditions induced the degradation of flavonoids, which contributed to environmental stress amelioration. Moreover, a higher absorption peak of 360−380 nm UV was observed in the extract liquor of OP. The sensitivity maximum of the UV-photoreceptor of bees is situated around 340−380 nm UV. This suggested, as noted for the maximum absorption of dihydrokaempferol in 340−370 nm, rhythmic accumulation and loss of these differential flavonoids in Nymphaea ‘Blue Bird’ petals might enhance UV pattern to some degree, influencing pollinator attraction.

Redesign of (R)-Omega-Transaminase and Its Application for Synthesizing Amino Acids with Bulky Side Chain.

ω-Transaminase (ω-TA) is an attractive biocatalyst for stereospecific preparation of amino acids and derivatives, but low catalytic efficiency and unfavorable substrate specificity hamper their industrial application. In this work, to obtain applicable (R)-ω-TA responsible for amination of α-keto acids substrates, the reactivities of eight previously synthesized ω-TAs toward pyruvate using (R)-α-methylbenzylamine ((R)-α-MBA) as amine donor were investigated, and Gibberella zeae TA (GzTA) with the highest (R)-TA activity and stereoselectivity was selected as starting scaffold for engineering. Site-directed mutagenesis around enzymatic active pocket and access tunnel identified three positive mutation sites, S214A, F113L, and V60A. Kinetic analysis synchronously with molecular docking revealed that these mutations afforded desirable alleviation of steric hindrance for pyruvate and α-MBA. Furthermore, the constructed single-, double-, and triple-mutant exhibited varying degrees of improved specificities toward bulkier α-keto acids. Using 2-oxo-2-phenylacetic acid (1d) as substrate, the conversion rate of triple-mutant F113L/V60A/S214A increased by 3.8-fold relative to that of wide-type GzTA. This study provided a practical engineering strategy for improving catalytic efficiency and substrate specificity of (R)-ω-TA. The obtained experience shed light on creating more industrial ω-TAs mutants that can accommodate structurally diverse substrates.