L-glutamic acid(LA)is a bio-based,non-toxic,environmentally friendly material derived from biomass.The present study reports the application of Passerini three-component polymerization(P-3CP)for the straightforward pr...L-glutamic acid(LA)is a bio-based,non-toxic,environmentally friendly material derived from biomass.The present study reports the application of Passerini three-component polymerization(P-3CP)for the straightforward preparation of LA-based light-responsive polyesters(PLTDs)under mild conditions.PLTDs with molar masses up to 8500 g/mol and high yields exceeding 90%are obtained.The chemical structures and light-responsive self-immolative behavior of PLTDs are comprehensively characterized by employing ultraviolet-visible(UV-Vis)spectroscopy,size exclusion chromatography(SEC),nuclear magnetic resonance(NMR)spectroscopy,and liquid chromatography mass spectrometry(LC-MS).Meanwhile,monodisperse PLTD-based doxorubicin-loaded nanoparticles(PLTD-DOX-NP)(size=193 nm,PDI=0.018)are formulated by nanoprecipitation method.Upon light-induced depolymerization,the PLTD-DOX-NP undergoes rapid decomposition,resulting in a burst release of 80%cargo within 13 s.Furthermore,according to biological toxicity tests,the PLTD-NP possesses adequate biosafety,both before and after irradiation.Overall,the incorporation of P-3CP with biorenewable LA-based monomer adheres to the principles of green chemistry,significantly simplifying the synthetic pathway of light-responsive polymers.展开更多
The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymer...The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymeric carrier, a biodegradable linker and a bioactive anticancer agent, could form the basis of a new generation of anticancer agents. Poly （L-glutamic acid）- paclitaxel conjugate is a polymer-drug conjugate that links anticancer agent paclitaxel （PTX） to poly （L-glutamic acid） （PG）. PG-PTX conjugate can improve the anticancer activity, enhance the safety and efficacy, and improve the pharmacokinetic properties of PTX. Therefore, the application of PG-PTX facilitates the clinical therapy of a variety of human cancers.展开更多
Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficac...Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.展开更多
The preparation and characterization of an immobilized L-glutamic decarboxylase (GDC) were studied. This work is to develop a sensitive method for the determination of L-glutamate using a new biosensor, which consists...The preparation and characterization of an immobilized L-glutamic decarboxylase (GDC) were studied. This work is to develop a sensitive method for the determination of L-glutamate using a new biosensor, which consists of an enzyme column reactor of GDC immobilized on a novel ion exchange resin (carboxymethyl-copolymer of allyl dextran and N.N?methylene-bisacrylamide CM-CADB) and ion analyzer coupled with a CO2 electrode. The conditions for the enzyme immobilization were optimized by the parameters: buffer composition and concentration, adsorption equilibration time, amount of enzyme, temperature, ionic strength and pH. The properties of the immobilized enzyme on CM-CADB were studied by investigating the initial rate of the enzyme reaction, the effect of various parameters on the immobilized GDC activity and its stability. An immobilized GDC enzyme column reactor matched with a flow injection system-ion analyzer coupled with CO2 electrode-data collection system made up the original form of the apparatus of biosensor for determining of L-glutamate acid. The limit of detection is 1.0×10-5 M. The linearity response is in the range of 5×10 -2-5×10 -5 M . The equation of linear regression of the calibration curve is y= 43.3x + 181.6 (y is the milli-volt of electrical potential response, x is the logarithm of the concentration of the substrate of L-glutamate acid). The correlation coefficient equals 0.99. The coefficient of variation equals 2.7%.展开更多
PEGylation has been widely applied to prolong the circulation times of nanomedicines via the steric shielding effect,which consequently improves the intratumoral accumulation.However,cell uptake of PEGylated nanoformu...PEGylation has been widely applied to prolong the circulation times of nanomedicines via the steric shielding effect,which consequently improves the intratumoral accumulation.However,cell uptake of PEGylated nanoformulations is always blocked by the steric repulsion of PEG,which limits their therapeutic effect.To this end,we designed and prepared two kinds of poly(L-glutamic acid)-cisplatin(PLG-CDDP)nanoformulations with detachable PEG,which is responsive to specific tumor tissue microenvironments for prolonged circulation time and enhanced cell internalization.The extracellular pH(pHe)-responsive cleavage 2-propionic-3-methylmaleic anhydride(CDM)-derived amide bond and matrix metalloproteinases-2/9(MMP-2/9)-sensitive degradable peptide PLGLAG were utilized to link PLG and PEG,yielding pHe-responsive PEG-pHe-PLG and MMP-sensitive PEG-MMP-PLG.The corresponding smart nanoformulations PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were then prepared by the complexation of polypeptides and cisplatin(CDDP).The circulation half-lives of PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were about 4.6 and 4.2 times higher than that of the control PLG-Pt,respectively.Upon reaching tumor tissue,PEG on the surface of nanomedicines was detached as triggered by pHe or MMP,which increased intratumoral CDDP retention,enhanced cell uptake,and improved antitumor efficacy toward a fatal high-grade serous ovarian cancer(HGSOC)mouse model,indicating the promising prospects for clinical application of detachable PEGylated nanoformulations.展开更多
A concise synthesis of the mosquito oviposition attractant pheromone, (-)-(5R, 6S)- and (+)-(5S 6R)-6-acetoxy hexadecanolide from L-glutamic acid is described. The key steps are the inversion of the configuration at C...A concise synthesis of the mosquito oviposition attractant pheromone, (-)-(5R, 6S)- and (+)-(5S 6R)-6-acetoxy hexadecanolide from L-glutamic acid is described. The key steps are the inversion of the configuration at C-4 of 7, and the formation of δ-lactone from the γ-lactone through ring enlargement.展开更多
A rare earth coordination system was first investigated as a new type of catalyst for the ring-openingpolymerization of α-amino acid N-carboxyanhydrides (NCAs). The results for the polymerization of γ-stearyl-α,L-g...A rare earth coordination system was first investigated as a new type of catalyst for the ring-openingpolymerization of α-amino acid N-carboxyanhydrides (NCAs). The results for the polymerization of γ-stearyl-α,L-glutamate(SLG) NCA using neodymium acetylacetonate (Nd(acac)_3)- or neodymium tris(2-ethylhexylphosphonate) (Nd(P_(204))_3)-triethylaluminum-water as catalysts were compared with those using conventional catalysts. It was found that the helicalpoly(γ-stearyl-L-glutamate) with high molecular weight as well as narrow molecular weight distribution can be obtained inthe presence of Nd(acac)_3/AlEt_3-1/2H_2O. The polymer obtained was characterized by IR and NMR spectroscopy.展开更多
Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus ...Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.展开更多
Near-infrared spectroscopy （NIRS） with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares （PLS） r...Near-infrared spectroscopy （NIRS） with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares （PLS） regression can be used as a rapid analytical method to simultaneously quantify L-glutamic acid （L- GIu） and γ-aminobutyric acid （GABA） in a biotransformation process and to guide the optimization of production conditions when the merits of NIRS are combined with response surface methodology. The high performance liquid chromatography （HPLC） reference analysis was performed by the o-phthaldialdehyde pre-column derivatization. NIRS measurements of two batches of 141 samples were firstly analyzed by PLS with several spectral pre-processing methods. Compared with those of the HPLC reference analysis, the resulting determination coefficients （R2）, root mean square error of prediction （RMSEP） and residual predictive deviation （RPD） of the external validation for the L-GIu concentration were 99.5%, 1.62 g/L, and 11.3, respectively. For the GABA concentration, R2, RMSEP, and RPD were 99.8%, 4.00 g/L, and 16.4, respectively. This NIRS model was then used to optimize the biotransformation process through a Box- Behnken experimental design. Under the optimal conditions without pH adjustment, 200 gjL L-GIu could be catalyzed by 7148 U/L glutamate decarboxylase （GAD） to GABA, reaching 99% conversion at the fifth hour. NIRS analysis provided timely information on the conversion from L-GIu to GABA. The results suggest that the NIRS model can not only be used for the routine profiling of enzymatic conversion, providing a simple and effective method of monitoring the biotransformation process of GABA, but also be considered to be an optimal tool to guide the optimization of production conditions.展开更多
Self-healing hydrogels with the shear-thinning property are novel injectable materials and are superior to traditional injectable hydrogels.The self-healing hydrogels based on 2-ureido-4[1 H]-pyrimidinone(UPy)have rec...Self-healing hydrogels with the shear-thinning property are novel injectable materials and are superior to traditional injectable hydrogels.The self-healing hydrogels based on 2-ureido-4[1 H]-pyrimidinone(UPy)have recently received extensive attention due to their dynamic reversibility of UPy dimerization.However,generally,UPy-based self-healing hydrogels exhibit poor stability,cannot degrade in vivo and can hardly be excreted from the body,which considerably limit their bio-application.Here,using poly(l-glutamic acid)(PLGA)as biodegradable matrix,branchingα-hydroxy-ω-amino poly(ethylene oxide)(HAPEO)as bridging molecule to introduce UPy,and ethyl acrylate polyethylene glycol(MAPEG)to introduce double bond,the hydrogel precursors(PMHU)are prepared.A library of the self-healing hydrogels has been achieved with well self-healable and shear-thinning properties.With the increase of MAPEG grafting ratio,the storage modulus of the self-healing hydrogels decreases.The self-healing hydrogels are stable in solution only for 6 h,hard to meet the requirements of tissue regeneration.Consequently,ultraviolet(UV)photo-crosslinking is involved to obtain the dual crosslinking hydrogels with enhanced mechanical properties and stability.When MAPEG grafting ratio is 35.5%,the dual crosslinking hydrogels can maintain the shape in phosphate-buffered saline solution(PBS)for at least 8 days.Loading with adipose-derived stem cell spheroids,the self-healing hydrogels are injected and self-heal to a whole,and then they are crosslinked in situ via UV-irradiation,obtaining the dual crosslinking hydrogels/cell spheroids complex with cell viability of 86.7%±6.0%,which demonstrates excellent injectability,subcutaneous gelatinization,and biocompatibility of hydrogels as cell carriers.The novel PMHU hydrogels crosslinked by quadruple hydrogen bonding and then dual photo-crosslinking of double bond are expected to be applied for minimal invasive surgery or therapies in tissue engineering.展开更多
The purpose of this study were to confirm whether the modified treatment with L-glutamic acid could attenuate the calcification of the GA-fixed valves and improve its biocompatibility. Pericardial valves were routinel...The purpose of this study were to confirm whether the modified treatment with L-glutamic acid could attenuate the calcification of the GA-fixed valves and improve its biocompatibility. Pericardial valves were routinely treated with GA and valves were treated with GA and 8% L-glutamic acid. The valves treated with these methods were implanted subcutaneously in rats. Calcium deposits of the valves collected at the 7th, 21st, 60th, 90th day were assessed by atomic absorption spectroscopy, and the pathologic changes were examined by light and electron microscopy. Cultured endothelial cells (ECs ) were seeded onto the valves. The cell counts were determined at the 1st. 4th, 7th, 10th day after seeding. PGI2 in culture medium was tested at the 10th day. Transmission and scanning electron microscopy were used to observe the growth of ECs on the valves.Results showed that subsequent treatment with L-glutamic acid could significantly mitigate calcification of bovine pericardial valves as compared with simple GAfixed valves (P<0. 01). ECs seeded on the GA treated valves died within 4 days.On the valves treated by modified method, ECs could proliferate and release PGI2. It is concluded that treatment with L- glutamic acid can markedly inhibit the calcification and improve the biocompatibility of bioprosthetical valves.展开更多
Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glut...Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.展开更多
[Objective]The paper was to investigate the effect of dietary supplementation of Fu-libao and L-glutamic acid on finishing and slaughter performances and meat quality trait of"L(Large Yorkshire)×L(Landrace)&...[Objective]The paper was to investigate the effect of dietary supplementation of Fu-libao and L-glutamic acid on finishing and slaughter performances and meat quality trait of"L(Large Yorkshire)×L(Landrace)"crossbred pigs.[Method]Twelve individuals of L×L crossbred pigs with similar body weight of about 51 kg were selected.The pigs were randomly divided into two groups,three replicates each group,two piglets each replicate.The pigs in control group were fed with conventional diet(control diet),and pigs in treatment group were fed with the control diet added with 0.1%Fu-libao(mainly contained soybean phospholipid)and 0.6%L-glutamic acid.All the pigs were under the same feeding conditions except for different diets during the trial.At the end of the trial,one pig with similar body weight was selected from each replicate for slaughter and determination of meat quality.[Result]Dietary supplementation of Fu-libao and L-glutamic acid had no significant impact on finishing performance of pigs between the two groups(P>0.05),but the back fat thickness of pigs in treatment group was increased(P<0.05).On the contrary,the longissimus muscle(LM)area,meat color and water-holding capacity(WHC)were reduced significantly compared with the control group(P<0.05).However,the contents of glutamic acid,glysine,alanine,threonine,proline,valine and arginine in LM were increased significantly compared with the control group(P<0.05);moreover,the total amino acid and total flavor amino acid contents in LM were increased by 5.85%(P<0.05)and 6.87%(P<0.05)respectively.In addition,the content of intramuscular fat(IMF)in LM was improved from 5.11±0.24(control group)to 8.86±0.52(treatment group)(P<0.05).[Conclusion]Although dietary supplementation of Fu-libao and L-glutamic acid did not increase the finishing and slaughter performances of L×L crossbred pigs,it significantly enhanced the contents of total amino acid,total flavor amino acid and IMF,and significantly improved meat quality.展开更多
Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-t...Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine on feed intake and the mRNA expression levels of hypothalamic Neuropeptide involved in feed intake regulation in broiler chicks. Leucine, glutamate, tryptophan or arginine was intra-cerebroventricularly （ICV） administrated to 4d-old broiler chicks respectively and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of Neuropeptide Y （NPY）, agouti related protein （AgRP）, pro-opiomelanocortin （POMC）, melanocortin receptor 4 （MC4R） and corticotrophin releasing factor （CRF）. Our results showed that ICV administration of L-leucine （0.15 or 1.5 μmol） significantly （P〈0.05） increased feed intake up to 2 h post-administration period and elevated both hypothalamic NPY and AgRP mRNA expression levels. In contrast, ICV administration of L-glutamate （1.6 μmol） significantly （P 〈 0.05） decreased feed intake 0.25, 0.5 and 2 h post-injection, and increased hypothalamic CRF and MC4R mRNA expression levels. Meanwhile, both L-tryptophan （10 or 100 μg） and L-arginine （20 or 200 μg） had no significant effect on feed intake. These findings suggested that L-leucine and L-glutamate could act within the hypothalamus to influence food intake, and that both orexigenic and anorexigenic Neuropeptide genes might contribute directly to these effects.展开更多
Lead halide perovskite nanocrystals(NCs)exhibit excellent optoelectronic performance and have drawn great interests in the fields of biological imaging and sensing.However,the poor stability of CsPbX_(3)(X=Cl,Br,I)in ...Lead halide perovskite nanocrystals(NCs)exhibit excellent optoelectronic performance and have drawn great interests in the fields of biological imaging and sensing.However,the poor stability of CsPbX_(3)(X=Cl,Br,I)in water is still a challenge to hinder their practical applications.In this work,a facile strategy has been developed for aqueous synthesis of CsPbX_(3) nanocrystals,in which L-glutamic acid(LGlu)has been used to replace oleic acid in the synthetic process.Benefiting from the synergic effects of L-Glu and oleylamine(OAm),CsPbBr_(3)nanocrystals(L-Glu/OAm-CsPbBr_(3)NCs)with high water stability have been directly prepared under a mild condition at room temperature in water,facilitated by the process of crystal phase transformation from Cs_(4)PbBr_(6) to CsPbBr_(3).L-Glu/OAm-CsPbBr_(3)NCs exhibit a high quantum yield of 85%and a narrow full width at half maximum of 16 nm,demonstrating their efficient luminescence in water.Typically,L-Glu on the surface have contributed greatly to an acidic environment and passivation of surface defects,improving the water stability and dispersibility of CsPbBr_(3)nanocrystals.Moreover,L-Glu/OAm-CsPbBr_(3)NCs exhibit great biocompatibility due to the presence of L-Glu,resulting in their good performance for HeLa cell imaging.Thus,we propose a facile and effective method to prepare CsPbBr_(3)nanocrystals with excellent water stability by using L-Glu and OAm as cooperated ligands and expand their application in cell imaging.展开更多
Background L-glutamate （L-GLU） is a major neurotransmitter in the nucleus ambiguus （NA）, which can modulate respiration, arterial pressure, heart rate, etc. This study investigated the effects and mechanisms of L-...Background L-glutamate （L-GLU） is a major neurotransmitter in the nucleus ambiguus （NA）, which can modulate respiration, arterial pressure, heart rate, etc. This study investigated the effects and mechanisms of L-GLU microinjected into NA on gastric motility in rats. Methods A latex balloon connected with a pressure transducer was inserted into the pylorus through the forestomach for continuous recording of the gastric motility. The total amplitude, total duration, and motility index of gastric contraction waves within 5 minutes before microinjection and after microinjection were measured. Results L-GLU （5 nmol, 10 nmol and 20 nmol in 50 nl normal saline （PS） respectively） microinjected into the right NA significantly inhibited gastric motility, while microinjection of physiological saline at the same position and the same volume did not change the gastric motility. The inhibitory effect was blocked by D-2-amino-5-phophonovalerate （D-AP5, 5 nmol, in 50 nl PS）, the specific N-methyI-D-aspartic acid （NMDA） receptor antagonist, but was not influenced by 6-cyaon-7-nitroquinoxaline-2,3-（1H,4H）-dione （CNQX） （5 nmol, in 50 nl PS）, the non-NMDA ionotropic receptor antagonist. Bilateral subdiaphragmatic vagotomy abolished the inhibitory effect by microinjection of L-GLU into NA. Conclusions Microinjection of L-GLU into NA inhibits the gastric motility through specific NMDA receptor activity, not non-NMDA receptor activity, and the efferent pathway is the vagal nerves.展开更多
L-glutamate family amino acids(GFAAs),consisting of L-glutamate,L-arginine,L-citrulline,L-ornithine,L-proline,L-hydroxyproline,γ-aminobutyric acid,and 5-aminolevulinic acid,are widely applied in the food,pharmaceutic...L-glutamate family amino acids(GFAAs),consisting of L-glutamate,L-arginine,L-citrulline,L-ornithine,L-proline,L-hydroxyproline,γ-aminobutyric acid,and 5-aminolevulinic acid,are widely applied in the food,pharmaceutical,cosmetic,and animal feed industries,accounting for billions of dollars of market activity.These GFAAs have many functions,including being protein constituents,maintaining the urea cycle,and providing precursors for the biosynthesis of pharmaceuticals.Currently,the production of GFAAs mainly depends on microbial fermentation using Corynebacterium glutamicum(including its related subspecies Corynebacterium crenatum),which is substantially engineered through multistep metabolic engineering strategies.This review systematically summarizes recent advances in the metabolic pathways,regulatory mechanisms,and metabolic engineering strategies for GFAA accumulation in C.glutamicum and C.crenatum,which provides insights into the recent progress in L-glutamate-derived chemical production.展开更多
基金This work was financially supported by the International Science and Technology Assistance Program of the Ministry of Science and Technology(No.KY202001016)Shandong Provincial Natural Science Foundation Magnitude Fundamental Research,China(No.ZR2022ZD11)Qingdao New Energy Shandong Laboratory Open Project(No.QNESL OP202312).
文摘L-glutamic acid(LA)is a bio-based,non-toxic,environmentally friendly material derived from biomass.The present study reports the application of Passerini three-component polymerization(P-3CP)for the straightforward preparation of LA-based light-responsive polyesters(PLTDs)under mild conditions.PLTDs with molar masses up to 8500 g/mol and high yields exceeding 90%are obtained.The chemical structures and light-responsive self-immolative behavior of PLTDs are comprehensively characterized by employing ultraviolet-visible(UV-Vis)spectroscopy,size exclusion chromatography(SEC),nuclear magnetic resonance(NMR)spectroscopy,and liquid chromatography mass spectrometry(LC-MS).Meanwhile,monodisperse PLTD-based doxorubicin-loaded nanoparticles(PLTD-DOX-NP)(size=193 nm,PDI=0.018)are formulated by nanoprecipitation method.Upon light-induced depolymerization,the PLTD-DOX-NP undergoes rapid decomposition,resulting in a burst release of 80%cargo within 13 s.Furthermore,according to biological toxicity tests,the PLTD-NP possesses adequate biosafety,both before and after irradiation.Overall,the incorporation of P-3CP with biorenewable LA-based monomer adheres to the principles of green chemistry,significantly simplifying the synthetic pathway of light-responsive polymers.
基金National Key Technologies R&D Program for New Drugs(Grant No.2009ZX09301-002,2009ZX09304-004).
文摘The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymeric carrier, a biodegradable linker and a bioactive anticancer agent, could form the basis of a new generation of anticancer agents. Poly （L-glutamic acid）- paclitaxel conjugate is a polymer-drug conjugate that links anticancer agent paclitaxel （PTX） to poly （L-glutamic acid） （PG）. PG-PTX conjugate can improve the anticancer activity, enhance the safety and efficacy, and improve the pharmacokinetic properties of PTX. Therefore, the application of PG-PTX facilitates the clinical therapy of a variety of human cancers.
基金supported by National Natural Science Foundation of China (No. 51373168)
文摘Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.
基金The Applied Fundamental Foundation of Jiangsu province P. R. China. Contract No BJ98041.
文摘The preparation and characterization of an immobilized L-glutamic decarboxylase (GDC) were studied. This work is to develop a sensitive method for the determination of L-glutamate using a new biosensor, which consists of an enzyme column reactor of GDC immobilized on a novel ion exchange resin (carboxymethyl-copolymer of allyl dextran and N.N?methylene-bisacrylamide CM-CADB) and ion analyzer coupled with a CO2 electrode. The conditions for the enzyme immobilization were optimized by the parameters: buffer composition and concentration, adsorption equilibration time, amount of enzyme, temperature, ionic strength and pH. The properties of the immobilized enzyme on CM-CADB were studied by investigating the initial rate of the enzyme reaction, the effect of various parameters on the immobilized GDC activity and its stability. An immobilized GDC enzyme column reactor matched with a flow injection system-ion analyzer coupled with CO2 electrode-data collection system made up the original form of the apparatus of biosensor for determining of L-glutamate acid. The limit of detection is 1.0×10-5 M. The linearity response is in the range of 5×10 -2-5×10 -5 M . The equation of linear regression of the calibration curve is y= 43.3x + 181.6 (y is the milli-volt of electrical potential response, x is the logarithm of the concentration of the substrate of L-glutamate acid). The correlation coefficient equals 0.99. The coefficient of variation equals 2.7%.
基金The study was financially supported by the National Natural Science Foundation of China(Grant Nos.52073280,51973216,and 51673187).
文摘PEGylation has been widely applied to prolong the circulation times of nanomedicines via the steric shielding effect,which consequently improves the intratumoral accumulation.However,cell uptake of PEGylated nanoformulations is always blocked by the steric repulsion of PEG,which limits their therapeutic effect.To this end,we designed and prepared two kinds of poly(L-glutamic acid)-cisplatin(PLG-CDDP)nanoformulations with detachable PEG,which is responsive to specific tumor tissue microenvironments for prolonged circulation time and enhanced cell internalization.The extracellular pH(pHe)-responsive cleavage 2-propionic-3-methylmaleic anhydride(CDM)-derived amide bond and matrix metalloproteinases-2/9(MMP-2/9)-sensitive degradable peptide PLGLAG were utilized to link PLG and PEG,yielding pHe-responsive PEG-pHe-PLG and MMP-sensitive PEG-MMP-PLG.The corresponding smart nanoformulations PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were then prepared by the complexation of polypeptides and cisplatin(CDDP).The circulation half-lives of PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were about 4.6 and 4.2 times higher than that of the control PLG-Pt,respectively.Upon reaching tumor tissue,PEG on the surface of nanomedicines was detached as triggered by pHe or MMP,which increased intratumoral CDDP retention,enhanced cell uptake,and improved antitumor efficacy toward a fatal high-grade serous ovarian cancer(HGSOC)mouse model,indicating the promising prospects for clinical application of detachable PEGylated nanoformulations.
文摘A concise synthesis of the mosquito oviposition attractant pheromone, (-)-(5R, 6S)- and (+)-(5S 6R)-6-acetoxy hexadecanolide from L-glutamic acid is described. The key steps are the inversion of the configuration at C-4 of 7, and the formation of δ-lactone from the γ-lactone through ring enlargement.
基金This work was supported by National Natural Science Foundation of China (No. 29504029).
文摘A rare earth coordination system was first investigated as a new type of catalyst for the ring-openingpolymerization of α-amino acid N-carboxyanhydrides (NCAs). The results for the polymerization of γ-stearyl-α,L-glutamate(SLG) NCA using neodymium acetylacetonate (Nd(acac)_3)- or neodymium tris(2-ethylhexylphosphonate) (Nd(P_(204))_3)-triethylaluminum-water as catalysts were compared with those using conventional catalysts. It was found that the helicalpoly(γ-stearyl-L-glutamate) with high molecular weight as well as narrow molecular weight distribution can be obtained inthe presence of Nd(acac)_3/AlEt_3-1/2H_2O. The polymer obtained was characterized by IR and NMR spectroscopy.
文摘Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.
基金supported by the National Natural Science Foundation of China (Nos. 81374046 and 81373506)
文摘Near-infrared spectroscopy （NIRS） with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares （PLS） regression can be used as a rapid analytical method to simultaneously quantify L-glutamic acid （L- GIu） and γ-aminobutyric acid （GABA） in a biotransformation process and to guide the optimization of production conditions when the merits of NIRS are combined with response surface methodology. The high performance liquid chromatography （HPLC） reference analysis was performed by the o-phthaldialdehyde pre-column derivatization. NIRS measurements of two batches of 141 samples were firstly analyzed by PLS with several spectral pre-processing methods. Compared with those of the HPLC reference analysis, the resulting determination coefficients （R2）, root mean square error of prediction （RMSEP） and residual predictive deviation （RPD） of the external validation for the L-GIu concentration were 99.5%, 1.62 g/L, and 11.3, respectively. For the GABA concentration, R2, RMSEP, and RPD were 99.8%, 4.00 g/L, and 16.4, respectively. This NIRS model was then used to optimize the biotransformation process through a Box- Behnken experimental design. Under the optimal conditions without pH adjustment, 200 gjL L-GIu could be catalyzed by 7148 U/L glutamate decarboxylase （GAD） to GABA, reaching 99% conversion at the fifth hour. NIRS analysis provided timely information on the conversion from L-GIu to GABA. The results suggest that the NIRS model can not only be used for the routine profiling of enzymatic conversion, providing a simple and effective method of monitoring the biotransformation process of GABA, but also be considered to be an optimal tool to guide the optimization of production conditions.
基金financially supported by the National Natural Science Foundation of China(No.51773113)。
文摘Self-healing hydrogels with the shear-thinning property are novel injectable materials and are superior to traditional injectable hydrogels.The self-healing hydrogels based on 2-ureido-4[1 H]-pyrimidinone(UPy)have recently received extensive attention due to their dynamic reversibility of UPy dimerization.However,generally,UPy-based self-healing hydrogels exhibit poor stability,cannot degrade in vivo and can hardly be excreted from the body,which considerably limit their bio-application.Here,using poly(l-glutamic acid)(PLGA)as biodegradable matrix,branchingα-hydroxy-ω-amino poly(ethylene oxide)(HAPEO)as bridging molecule to introduce UPy,and ethyl acrylate polyethylene glycol(MAPEG)to introduce double bond,the hydrogel precursors(PMHU)are prepared.A library of the self-healing hydrogels has been achieved with well self-healable and shear-thinning properties.With the increase of MAPEG grafting ratio,the storage modulus of the self-healing hydrogels decreases.The self-healing hydrogels are stable in solution only for 6 h,hard to meet the requirements of tissue regeneration.Consequently,ultraviolet(UV)photo-crosslinking is involved to obtain the dual crosslinking hydrogels with enhanced mechanical properties and stability.When MAPEG grafting ratio is 35.5%,the dual crosslinking hydrogels can maintain the shape in phosphate-buffered saline solution(PBS)for at least 8 days.Loading with adipose-derived stem cell spheroids,the self-healing hydrogels are injected and self-heal to a whole,and then they are crosslinked in situ via UV-irradiation,obtaining the dual crosslinking hydrogels/cell spheroids complex with cell viability of 86.7%±6.0%,which demonstrates excellent injectability,subcutaneous gelatinization,and biocompatibility of hydrogels as cell carriers.The novel PMHU hydrogels crosslinked by quadruple hydrogen bonding and then dual photo-crosslinking of double bond are expected to be applied for minimal invasive surgery or therapies in tissue engineering.
文摘The purpose of this study were to confirm whether the modified treatment with L-glutamic acid could attenuate the calcification of the GA-fixed valves and improve its biocompatibility. Pericardial valves were routinely treated with GA and valves were treated with GA and 8% L-glutamic acid. The valves treated with these methods were implanted subcutaneously in rats. Calcium deposits of the valves collected at the 7th, 21st, 60th, 90th day were assessed by atomic absorption spectroscopy, and the pathologic changes were examined by light and electron microscopy. Cultured endothelial cells (ECs ) were seeded onto the valves. The cell counts were determined at the 1st. 4th, 7th, 10th day after seeding. PGI2 in culture medium was tested at the 10th day. Transmission and scanning electron microscopy were used to observe the growth of ECs on the valves.Results showed that subsequent treatment with L-glutamic acid could significantly mitigate calcification of bovine pericardial valves as compared with simple GAfixed valves (P<0. 01). ECs seeded on the GA treated valves died within 4 days.On the valves treated by modified method, ECs could proliferate and release PGI2. It is concluded that treatment with L- glutamic acid can markedly inhibit the calcification and improve the biocompatibility of bioprosthetical valves.
基金Funding support was from the Novo Nordisk Foundation with the project's grant number NNFSA210073688.
文摘Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.
基金Major Special Project of Science and Technology Innovation-driven Development in Guangxi Province(GK AA17204052)Special Project of Basic Scientific Research Operating Expenses of Directly Affiliated Public-Interest Research Institutions in Guangxi Province(GMYK 2019-9)Special Fund Project of Central Government Guiding the Development of Local Science and Technology(GK ZY18076011).
文摘[Objective]The paper was to investigate the effect of dietary supplementation of Fu-libao and L-glutamic acid on finishing and slaughter performances and meat quality trait of"L(Large Yorkshire)×L(Landrace)"crossbred pigs.[Method]Twelve individuals of L×L crossbred pigs with similar body weight of about 51 kg were selected.The pigs were randomly divided into two groups,three replicates each group,two piglets each replicate.The pigs in control group were fed with conventional diet(control diet),and pigs in treatment group were fed with the control diet added with 0.1%Fu-libao(mainly contained soybean phospholipid)and 0.6%L-glutamic acid.All the pigs were under the same feeding conditions except for different diets during the trial.At the end of the trial,one pig with similar body weight was selected from each replicate for slaughter and determination of meat quality.[Result]Dietary supplementation of Fu-libao and L-glutamic acid had no significant impact on finishing performance of pigs between the two groups(P>0.05),but the back fat thickness of pigs in treatment group was increased(P<0.05).On the contrary,the longissimus muscle(LM)area,meat color and water-holding capacity(WHC)were reduced significantly compared with the control group(P<0.05).However,the contents of glutamic acid,glysine,alanine,threonine,proline,valine and arginine in LM were increased significantly compared with the control group(P<0.05);moreover,the total amino acid and total flavor amino acid contents in LM were increased by 5.85%(P<0.05)and 6.87%(P<0.05)respectively.In addition,the content of intramuscular fat(IMF)in LM was improved from 5.11±0.24(control group)to 8.86±0.52(treatment group)(P<0.05).[Conclusion]Although dietary supplementation of Fu-libao and L-glutamic acid did not increase the finishing and slaughter performances of L×L crossbred pigs,it significantly enhanced the contents of total amino acid,total flavor amino acid and IMF,and significantly improved meat quality.
基金supported by National Key Project(2009CB941601)the Joint Funds of the National Natural Science Foundation of China(u0731004)+3 种基金National Natural Science Foundation of China(30871845,30901058 and 30972157)the Natural Science Foundation of Guangdong Province of China(9451064201003790 and 9151064201000056)the Special Fund for Agro-scientific Research in the Public Interest(201003011)Specialized Research Fund for the Doctoral Program of Higher Education of China(20094404120012)
文摘Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine on feed intake and the mRNA expression levels of hypothalamic Neuropeptide involved in feed intake regulation in broiler chicks. Leucine, glutamate, tryptophan or arginine was intra-cerebroventricularly （ICV） administrated to 4d-old broiler chicks respectively and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of Neuropeptide Y （NPY）, agouti related protein （AgRP）, pro-opiomelanocortin （POMC）, melanocortin receptor 4 （MC4R） and corticotrophin releasing factor （CRF）. Our results showed that ICV administration of L-leucine （0.15 or 1.5 μmol） significantly （P〈0.05） increased feed intake up to 2 h post-administration period and elevated both hypothalamic NPY and AgRP mRNA expression levels. In contrast, ICV administration of L-glutamate （1.6 μmol） significantly （P 〈 0.05） decreased feed intake 0.25, 0.5 and 2 h post-injection, and increased hypothalamic CRF and MC4R mRNA expression levels. Meanwhile, both L-tryptophan （10 or 100 μg） and L-arginine （20 or 200 μg） had no significant effect on feed intake. These findings suggested that L-leucine and L-glutamate could act within the hypothalamus to influence food intake, and that both orexigenic and anorexigenic Neuropeptide genes might contribute directly to these effects.
基金support from the National Natural Science Foundation of China(Nos.22221001,and 22131007)the Science and Technology Major Plan of Gansu Province(No.23ZDGA012)the 111 project(No.B20027).
文摘Lead halide perovskite nanocrystals(NCs)exhibit excellent optoelectronic performance and have drawn great interests in the fields of biological imaging and sensing.However,the poor stability of CsPbX_(3)(X=Cl,Br,I)in water is still a challenge to hinder their practical applications.In this work,a facile strategy has been developed for aqueous synthesis of CsPbX_(3) nanocrystals,in which L-glutamic acid(LGlu)has been used to replace oleic acid in the synthetic process.Benefiting from the synergic effects of L-Glu and oleylamine(OAm),CsPbBr_(3)nanocrystals(L-Glu/OAm-CsPbBr_(3)NCs)with high water stability have been directly prepared under a mild condition at room temperature in water,facilitated by the process of crystal phase transformation from Cs_(4)PbBr_(6) to CsPbBr_(3).L-Glu/OAm-CsPbBr_(3)NCs exhibit a high quantum yield of 85%and a narrow full width at half maximum of 16 nm,demonstrating their efficient luminescence in water.Typically,L-Glu on the surface have contributed greatly to an acidic environment and passivation of surface defects,improving the water stability and dispersibility of CsPbBr_(3)nanocrystals.Moreover,L-Glu/OAm-CsPbBr_(3)NCs exhibit great biocompatibility due to the presence of L-Glu,resulting in their good performance for HeLa cell imaging.Thus,we propose a facile and effective method to prepare CsPbBr_(3)nanocrystals with excellent water stability by using L-Glu and OAm as cooperated ligands and expand their application in cell imaging.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 30770277 and No. 30970354）.
文摘Background L-glutamate （L-GLU） is a major neurotransmitter in the nucleus ambiguus （NA）, which can modulate respiration, arterial pressure, heart rate, etc. This study investigated the effects and mechanisms of L-GLU microinjected into NA on gastric motility in rats. Methods A latex balloon connected with a pressure transducer was inserted into the pylorus through the forestomach for continuous recording of the gastric motility. The total amplitude, total duration, and motility index of gastric contraction waves within 5 minutes before microinjection and after microinjection were measured. Results L-GLU （5 nmol, 10 nmol and 20 nmol in 50 nl normal saline （PS） respectively） microinjected into the right NA significantly inhibited gastric motility, while microinjection of physiological saline at the same position and the same volume did not change the gastric motility. The inhibitory effect was blocked by D-2-amino-5-phophonovalerate （D-AP5, 5 nmol, in 50 nl PS）, the specific N-methyI-D-aspartic acid （NMDA） receptor antagonist, but was not influenced by 6-cyaon-7-nitroquinoxaline-2,3-（1H,4H）-dione （CNQX） （5 nmol, in 50 nl PS）, the non-NMDA ionotropic receptor antagonist. Bilateral subdiaphragmatic vagotomy abolished the inhibitory effect by microinjection of L-GLU into NA. Conclusions Microinjection of L-GLU into NA inhibits the gastric motility through specific NMDA receptor activity, not non-NMDA receptor activity, and the efferent pathway is the vagal nerves.
基金This work was supported by National Natural Science Foundation of China[No.32000057]Open Funding Project of the State Key Laboratory of Biocatalysis and Enzyme Engineering(SKLBEE2019015)+1 种基金Jiangxi Provincial Natural Science Foundation(No.20202BAB213023)Jiangxi Province Postgraduate Innovation Special Fund Project[No.YC2020-S258].
文摘L-glutamate family amino acids(GFAAs),consisting of L-glutamate,L-arginine,L-citrulline,L-ornithine,L-proline,L-hydroxyproline,γ-aminobutyric acid,and 5-aminolevulinic acid,are widely applied in the food,pharmaceutical,cosmetic,and animal feed industries,accounting for billions of dollars of market activity.These GFAAs have many functions,including being protein constituents,maintaining the urea cycle,and providing precursors for the biosynthesis of pharmaceuticals.Currently,the production of GFAAs mainly depends on microbial fermentation using Corynebacterium glutamicum(including its related subspecies Corynebacterium crenatum),which is substantially engineered through multistep metabolic engineering strategies.This review systematically summarizes recent advances in the metabolic pathways,regulatory mechanisms,and metabolic engineering strategies for GFAA accumulation in C.glutamicum and C.crenatum,which provides insights into the recent progress in L-glutamate-derived chemical production.
