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Polyglutamic acid

Poly-γ-glutamic acid (γ-PGA), commonly referred to as polyglutamic acid, is a naturally occurring, anionic homopolyamide biopolymer composed of repeating D- and L-glutamic acid monomers linked through amide bonds between the α-amino group and the γ-carboxylic acid group of adjacent units.^[1] This structure results in a flexible, water-soluble chain with molecular weights typically ranging from 10⁵ to 10⁷ Da, distinguishing it from other polyamino acids like poly-α-glutamic acid.^[2] Produced primarily by Gram-positive bacteria such as Bacillus subtilis and Bacillus licheniformis via microbial fermentation, γ-PGA is biodegradable, non-toxic, edible, and biocompatible, making it a versatile material for industrial and biomedical uses.^[3] The biosynthesis of γ-PGA occurs through a multi-step enzymatic pathway involving glutamate racemase (RacE or Glr) for converting L-glutamic acid to its D-form, followed by polymerization catalyzed by polyglutamate synthetase complex (PgsBCA) in the bacterial membrane.^[1] Production yields can reach up to over 120 g/L under optimized conditions as of 2024, such as neutral pH (6.5–7.5), aerobic fermentation with carbon sources like glucose or glycerol, and nitrogen supplements including L-glutamic acid.^[2]^[4] Recent optimizations using low-cost substrates like sugarcane molasses have further enhanced yields and sustainability.^[5] Genetic engineering of producer strains, including overexpression of key genes like pgsBCA and disruption of degradation enzymes (e.g., PgdS), has significantly enhanced efficiency and reduced production costs, which remain a challenge due to substrate expenses.^[6] Alternative methods, such as solid-state fermentation using agricultural wastes like soybean residue, promote sustainability and eco-friendliness.^[7] Key properties of γ-PGA include exceptional water absorption (up to 5000 times its weight), metal chelation due to abundant carboxyl groups, and resistance to proteases, alongside antimicrobial and antioxidant activities observed in vitro.^[8]^[3] These attributes stem from its polyanionic nature and stereochemical composition, which can be tailored (e.g., L-, D-, or alternating LD-forms) to suit specific applications.^[2] In medicine, γ-PGA serves as a carrier for targeted drug delivery, such as in conjugates with anticancer agents like paclitaxel, enhancing solubility and reducing toxicity while promoting tumor-specific uptake via EPR effect.^[1] It also supports tissue engineering scaffolds and wound dressings due to its biocompatibility and ability to accelerate healing.^[9] In cosmetics, γ-PGA acts as a humectant superior to hyaluronic acid in moisture retention, improving skin barrier function and reducing signs of aging.^[3] Agricultural uses leverage its role as a fertilizer synergist and plant growth promoter by enhancing nutrient uptake (e.g., N, P, K) and soil structure.^[1] Environmentally, it functions as a flocculant for wastewater treatment and biosorbent for heavy metals like Cr(VI) and Cu²⁺, with adsorption capacities up to 9–20 mg/g.^[9] In food, γ-PGA is employed as a thickener, cryoprotectant, and bitterness masker, ensuring safety as it is approved by regulatory bodies like the FDA for certain uses.^[2]

Structure and nomenclature

Chemical structure

Polyglutamic acid is a linear homopolymer formed by the polymerization of glutamic acid monomers, each with the molecular formula C₅H₉NO₄. The polymer has the formula (C₅H₇NO₃)ₙ.^[10] The repeating unit consists of the glutamic acid residue linked through amide bonds. In the α-form (α-PGA), the repeating unit is -[NH-CH(CH₂CH₂COOH)-CO]ₙ, yielding a standard polypeptide backbone with the γ-carboxyl as the side chain.^[11] Conversely, in the γ-form (γ-PGA), the more common natural variant, the repeating unit is -[NH-CH(COOH)-(CH₂)₂-CO]ₙ, with linkages between the γ-carboxyl group and the α-amino group, positioning the α-carboxyl as the side chain while maintaining the linear amide-connected chain.^[12] This structural distinction arises during biosynthesis but preserves the homopolymeric nature, with the side chain carboxyl group conferring polyanionic character regardless of linkage type.^[2] Natural polyglutamic acid typically has a molecular weight range of 10⁵ to 10⁷ Da, reflecting chain lengths that enhance macromolecular stability and functionality, with n typically ranging from several hundred to over 50,000.^[2] Higher molecular weights correspond to longer polymer chains (larger n values), which can influence conformational flexibility, though the fundamental repeating unit and bonding remain consistent.^[11]

Forms and stereochemistry

Polyglutamic acid (PGA) encompasses a family of biopolymers derived from glutamic acid monomers, with the primary distinction lying in the position of the amide linkage between repeating units. The two main forms are α-polyglutamic acid (α-PGA), which features peptide bonds between the α-amino and α-carboxyl groups of adjacent glutamic acid residues, and γ-polyglutamic acid (γ-PGA), characterized by bonds between the α-amino and γ-carboxyl groups.^[13] α-PGA is predominantly produced through chemical synthesis and consists mainly of L-glutamic acid units, whereas γ-PGA occurs naturally as an extracellular product of certain bacterial species and is the more prevalent form in biological contexts.^[8]^[11] Regarding stereochemistry, PGA variants can exist as homopolymers of either L- or D-glutamic acid or as copolymers incorporating both enantiomers in varying ratios. In microbial sources, γ-PGA often exhibits a racemic mixture or predominance of one enantiomer depending on the producing organism; for instance, Bacillus anthracis typically synthesizes poly-D-glutamic acid, while some Bacillus subtilis strains favor L-glutamic acid or alternating D/L configurations.^[8]^[11] This stereochemical diversity influences the polymer's conformational flexibility and interactions, with copolymers generally displaying enhanced solubility and reduced crystallinity compared to homopolymers.^[8] The historical identification of PGA traces back to the mid-20th century. In 1956, researchers isolated polyglutamic acid from the capsular material of Bacillus anthracis grown in vivo, establishing its structure as a key virulence factor and aggressin. Earlier, in 1942, the formation of an extracellular D-glutamic acid polypeptide during Bacillus subtilis fermentation was documented, later recognized as γ-PGA and notably associated with natto, the traditional Japanese fermented soybean product.^[14] A notable property differentiating the forms is the superior water solubility of γ-PGA, which arises from its γ-linkage that promotes a more extended, random coil conformation, thereby exposing hydrophilic carboxyl side chains and minimizing hydrophobic interactions along the backbone.^[13] In contrast, α-PGA tends to adopt more compact secondary structures, such as α-helices, under certain conditions, potentially limiting its solubility in aqueous environments.^[15] This enhanced solubility of γ-PGA contributes to its prevalence in natural microbial secretions and applications requiring dispersibility in water.^[2]

Properties

Physical properties

Polyglutamic acid (PGA) exhibits high water solubility, with aqueous solutions exceeding 100 g/L at neutral pH, due to its anionic polyelectrolyte structure that promotes dissociation and hydration in aqueous environments.^[2] This solubility is attributed to its anionic nature, which facilitates strong interactions with water molecules. Additionally, PGA is highly hygroscopic, capable of binding and retaining up to 5,000 times its weight in water, particularly for high molecular weight fractions exceeding 700 kDa, through hydrogen bonding via its polar carboxyl and amide groups.^[16] In solution, PGA forms a shear-thinning, non-Newtonian fluid, displaying pseudoplastic behavior where viscosity decreases under applied shear stress, making it suitable for flowable applications. Viscosity increases with molecular weight and concentration, reflecting its polyelectrolyte chain entanglement and ionic repulsion effects.^[8] PGA typically appears as a colorless to white powder in its dry form, which, when dissolved in water, yields a viscous gel-like aqueous solution due to its high molecular entanglement. It is fully biodegradable through enzymatic hydrolysis into non-toxic glutamic acid monomers without environmental persistence.^[2] Thermally, PGA demonstrates stability up to approximately 200°C, beyond which it undergoes depolymerization primarily via unzipping to form pyroglutamic acid, with major degradation occurring between 250–300°C depending on salt form and hydration state. Swelling behavior is pH-dependent, with greater expansion at neutral to basic pH due to deprotonation of carboxyl groups.^[17]^[18]

Chemical properties

Polyglutamic acid (PGA), particularly in its γ-form, functions as an anionic polyelectrolyte owing to its repeating glutamic acid units, each bearing a pendant carboxyl group with a pKa of approximately 4.3.^[19] At physiological pH around 7.4, these carboxyl groups are predominantly deprotonated, imparting a strong negative charge to the polymer chain and enabling electrostatic interactions with positively charged species.^[19] The chelating ability of PGA arises from its multiple carboxylate groups, which coordinate divalent cations such as Ca²⁺ and Mg²⁺ to form stable complexes. For instance, the binding constant for Ca²⁺ with PGA is approximately 6.5 × 10⁴ M⁻¹, corresponding to a log K value of about 4.8, with roughly 3-4 glutamate units coordinating one Ca²⁺ ion.^[20] This chelation enhances the solubility of these ions in aqueous environments and contributes to PGA's role in ion transport and stabilization. PGA exhibits excellent biocompatibility, characterized by its non-toxicity, with an oral LD50 exceeding 5 g/kg in rats, rendering it safe for ingestion.^[21] As an edible biopolymer derived from microbial sources like fermented soybeans, it is non-immunogenic and harmless to humans.^[11] Furthermore, PGA is biodegradable through enzymatic hydrolysis by proteases such as endo- and exo-γ-glutamyl peptidases, which cleave the γ-amide linkages in the polymer backbone.^[2] In addition to its ionic properties, PGA demonstrates pH buffering capacity in the range of 4.0 to 5.0, where the partial protonation of carboxyl groups allows it to resist significant pH shifts in mildly acidic conditions.^[22] This buffering, combined with its high water solubility, supports its utility in various formulations.^[22]

Natural occurrence and biosynthesis

Microbial sources

Polyglutamic acid, primarily in its γ-form, is naturally produced by several Gram-positive bacteria belonging to the genus Bacillus. The most prominent producers include Bacillus subtilis, particularly the natto strain used in traditional fermentation, Bacillus licheniformis, Bacillus anthracis in its capsular form, and emerging species such as Bacillus velezensis. These microorganisms synthesize γ-polyglutamic acid (γ-PGA) as an exopolymer, often under specific environmental stresses.^[2]^[23]^[24] In natural environments, γ-PGA serves as a key component of bacterial capsules and biofilms, providing protective functions. For instance, in B. anthracis, the poly-γ-D-glutamic acid capsule inhibits opsonization and phagocytosis by host immune cells, enabling survival within mammalian hosts. Bacillus species, including B. subtilis and B. velezensis, commonly inhabit soil and aquatic ecosystems, where γ-PGA contributes to biofilm matrix formation, enhancing microbial adhesion to surfaces and resilience in heterogeneous environments. These bacteria are frequently isolated from rhizosphere soils, water bodies, and fermented substrates, underscoring their ubiquity in terrestrial and aquatic niches.^[25]^[26]^[27] γ-PGA is notably abundant in certain fermented foods derived from Bacillus-mediated processes. In Japanese natto, produced by B. subtilis fermentation of soybeans, γ-PGA constitutes approximately 0.5-2% of the dry weight, responsible for the product's characteristic viscous mucilage. Trace amounts are also present in other Asian fermented soybean products, such as Korean cheonggukjang, where Bacillus strains contribute to similar textural properties, though at lower concentrations compared to natto.^[28]^[29] From an evolutionary perspective, γ-PGA plays a crucial role in microbial adaptation to harsh conditions, facilitating cell adhesion in biofilms and osmotic regulation through its hygroscopic properties, which help maintain hydration and ion balance in fluctuating soil and water habitats. This biopolymer enhances survival by promoting aggregation and protecting against desiccation and ionic stress in nutrient-poor or variable environments.^[26]^[30]

Biosynthetic pathways

Polyglutamic acid, specifically γ-polyglutamic acid (γ-PGA), is biosynthesized in certain Bacillus species through a multi-stage enzymatic process that incorporates both L- and D-isomers of glutamate into high-molecular-weight polymers. The pathway begins with the racemization of L-glutamate to produce the D-form, catalyzed by glutamate racemase encoded by the glr gene (or its isozymes racE and yrpC in Bacillus subtilis). This step is essential because the resulting γ-PGA typically consists of 20-80% D-glutamate residues, depending on the strain and conditions, enabling the formation of stable amide linkages between α-amino and γ-carboxyl groups.^[2]^[31] Polymerization follows, mediated by a membrane-bound polyglutamate synthase complex encoded by the pgsBCAE operon (or homologs such as ywsC, ywtC, ywtB, and ywtAB in B. subtilis). The complex includes PgsB (glutamyl poly-γ-glutamate synthetase), PgsC (catalytic subunit), PgsA (chain elongation), and PgsE (stabilizer), which assemble 100-1,000 glutamate units (or more in some cases) in an ATP-dependent manner. The process adds activated glutamate monomers to the growing chain via γ-linkages, with the simplified reaction represented as:

n \text{L-Glu} + n \text{ATP} \rightarrow [\gamma\text{-PGA}]_n + n \text{ADP} + n \text{P}_\text{i}

This occurs primarily using extracellular L-glutamic acid as the substrate, taken up by the cell, though an intracellular route via glutamine synthetase (GS) and glutamate synthase (GOGAT) can generate glutamate from glutamine and α-ketoglutarate under glutamate-independent conditions.^[2]^[31]^[8] Regulation of the pathway involves catabolic repression mechanisms, where glucose or other carbon sources inhibit γ-PGA synthesis through the DegS-DegU and ComP-ComA two-component systems, reducing expression of the pgs operon to prioritize energy metabolism. SwrA and DegQ proteins can modulate this, enhancing production under specific stresses like high pH or potassium levels. Degradation provides feedback control, with the endo-γ-glutamyl peptidase PgdS (encoded by pgdS) cleaving internal γ-PGA bonds to limit chain length, and γ-glutamyl transferase (Ggt, encoded by ggt or homolog pgdA in some strains) hydrolyzing exocyclic linkages to release monomers or oligomers for recycling. This four-stage process—racemization, polymerization, regulation, and degradation—ensures controlled accumulation of γ-PGA in the extracellular environment.^[2]^[31]

Production

Fermentation methods

Polyglutamic acid (PGA), particularly γ-PGA, is primarily produced through microbial fermentation using Bacillus species such as B. subtilis and B. licheniformis. Submerged fermentation represents the most common method for industrial-scale production, involving aerobic batch or fed-batch processes in stirred-tank bioreactors typically ranging from 5 to 50 L in laboratory settings, scalable to larger volumes for commercial use.^[11] Carbon sources like glucose or glycerol are utilized alongside L-glutamic acid as the primary nitrogen source, with typical conditions including a temperature of 37°C, pH maintained between 6.5 and 7.5, and agitation at 200–800 rpm to ensure adequate oxygen supply and prevent viscosity-related mass transfer issues.^[11] These parameters enable representative yields of around 40–100 g/L, depending on strain and medium composition.^[31] Solid-state fermentation offers an alternative approach, particularly for cost-sensitive applications, where microorganisms grow on solid substrates with minimal free water. Common substrates include soybean residue, wheat bran, or swine manure, which provide both nutrients and support, resulting in lower operational costs compared to submerged methods due to reduced equipment and wastewater needs.^[11] This process yields a higher viscosity product suitable for certain formulations and achieves up to 20–36 g/kg dry substrate, though it requires careful moisture control (typically 50–70%) and incubation at 30–37°C for 3–5 days.^[31] Downstream processing of PGA from fermentation broth begins with centrifugation or filtration to remove biomass, followed by precipitation using ethanol (often 2–4 volumes of cold ethanol added to the supernatant and held at 4°C overnight), which achieves recovery rates of 80–85%.^[13] The precipitate is then redissolved and purified via dialysis (using membranes with 12–14 kDa cutoff) against distilled water to remove salts and impurities, with overall recovery rates reaching 80–90% after lyophilization.^[13] Alternative precipitants like copper ions can enhance selectivity but are less commonly used due to residue concerns.^[31] The development of PGA fermentation methods traces back to lab-scale discoveries in the 1940s, when researchers identified PGA production in Bacillus anthracis capsules and B. subtilis cultures, initially studied for its role in bacterial virulence.^[32] Commercial production emerged in the 1990s in Japan, leveraging Bacillus strains from natto (fermented soybeans) for large-scale manufacturing, marking the shift to viable industrial processes.^[11]

Optimization techniques

Optimization of polyglutamic acid (PGA) production focuses on enhancing yield and product quality through targeted modifications in fermentation media, microbial strains, and process parameters, primarily using Bacillus species in submerged fermentation. Media optimization often involves the strategic addition of metal ions such as Mn²⁺, which stimulates microbial growth and PGA synthesis by influencing enzymatic activities in the biosynthetic pathway, leading to improved yields in Bacillus subtilis cultures. Similarly, surfactants like Tween 80 or surfactin co-production can enhance PGA secretion by reducing surface tension and improving oxygen transfer, as demonstrated in optimized Bacillus velezensis systems. Response surface methodology (RSM) is widely employed to fine-tune variables such as pH (typically 6.5–7.5) and temperature (35–37°C), resulting in yields of 50–100 g/L in Bacillus licheniformis and B. subtilis strains through factorial designs that maximize glutamate utilization and biomass accumulation.^[2]^[33]^[8] Strain engineering has significantly boosted PGA productivity by genetic manipulation of key biosynthetic and degradative genes. Overexpression of the pgsBCA operon, responsible for PGA polymerization, via plasmid integration in B. subtilis has increased yields by up to twofold compared to wild-type strains. CRISPR-Cas9-mediated editing, such as deletion of hydrolase genes like pgdS (encoding polyglutamate depolymerase) and ggt (gamma-glutamyltranspeptidase), prevents PGA degradation and achieves 2–3× higher yields, exceeding 40 g/L in engineered B. subtilis 168 derivatives. These modifications redirect metabolic flux toward PGA accumulation while maintaining cell viability.^[8]^[34]^[35] Recent advancements as of 2025 emphasize sustainable and cost-effective production using Bacillus velezensis strains, which offer eco-friendly alternatives due to their robustness and lower nutrient demands. Metabolic flux analysis integrated with glycerol as a low-cost carbon source has optimized carbon allocation in B. velezensis SDU, yielding 23.1 g/L PGA and reducing production costs by approximately 30% through efficient glycerol catabolism and reduced reliance on expensive glucose. These approaches combine transcriptomic data with flux modeling to enhance glutamate incorporation, supporting industrial scalability.^[36]^[37]^[38] Process controls in fed-batch fermentation further elevate yields by dynamically maintaining optimal conditions. pH-stat strategies, which automatically adjust pH through glutamate or base addition, sustain glutamate levels and prevent inhibition, achieving yields up to around 28 g/L in Bacillus systems, compared to wild-type yields of around 10 g/L. This method, combined with intermittent feeding of carbon and nitrogen sources, minimizes byproduct formation and maximizes PGA titer, as evidenced in large-scale bioreactors.^[39]^[8]^[2]

Applications

Biomedical applications

Polyglutamic acid (PGA) has garnered significant attention in biomedical applications due to its biocompatibility, biodegradability, and ability to form hydrogels and nanoparticles, making it suitable for therapeutic interventions. Its anionic nature facilitates interactions with biological molecules, enabling targeted delivery and tissue support without eliciting strong immune responses. These properties position PGA as a versatile polymer in medical contexts, particularly where controlled release and structural support are essential.^[40] In drug delivery, PGA conjugates with chemotherapeutic agents like doxorubicin (DOX) enhance targeted cancer therapy by exploiting the enhanced permeability and retention effect in tumors. For instance, PGA-DOX nanoparticles demonstrate pH-sensitive release at acidic tumor microenvironments (pH 5.8), achieving a tumor inhibition rate of 67.4% in models, which is 1.5 times higher than free DOX injections, while reducing systemic toxicity through slower clearance and lower cardiac accumulation. Similarly, paclitaxel conjugated to PGA (paclitaxel poliglumex) has shown complete tumor regression in murine models with improved pharmacokinetics, minimizing off-target effects compared to the free drug. Peptide-targeted PGA-DOX conjugates further improve specificity for αvβ6-positive cancers, enhancing cellular uptake and efficacy in preclinical studies.^[40]^[41] For tissue engineering, PGA-based scaffolds and hydrogels support wound healing and bone regeneration by providing a moist, biocompatible environment that promotes cell adhesion and proliferation. Composite scaffolds of collagen, PGA, and hydroxyapatite fabricated via 3D printing exhibit mechanical properties mimicking bone extracellular matrix, facilitating osteoblast differentiation and new bone formation in rat cranial defect models. Injectable PGA nanocomposites reduce bone defects by promoting mineralization and vascularization. Hydrogels combining hyaluronic acid and PGA maintain over 90% viability in NIH3T3 fibroblast cultures, enabling effective wound closure and tissue regeneration in diabetic models through enhanced cell migration and collagen deposition. Its biodegradability ensures safe implantation as the material degrades into non-toxic byproducts over time.^[40]^[42] Beyond these, PGA serves in biological glues for surgical applications, where combinations like N-hydroxysuccinimide-activated PGA with gelatin form strong adhesives that seal tissues with tensile strengths comparable to fibrin glues, reducing bleeding in preclinical wound models. As vaccine adjuvants, γ-PGA nanoparticles enhance immune responses by promoting antigen uptake and Th1/Th2 cytokine production, improving protection against influenza in animal studies when combined with alum. Antimicrobial coatings derived from PGA/ε-polylysine hydrogels inhibit pathogens like Staphylococcus aureus and Escherichia coli via cationic binding, achieving over 99% bacterial reduction on surfaces, suitable for implant coatings to prevent infections. Clinically, paclitaxel poliglumex conjugates advanced to phase III trials in the 2000s for ovarian and lung cancers, however, phase III trials did not lead to FDA approval. PGA-DOX remains under preclinical and early clinical investigation as of 2025, with ongoing investigations into nanoparticle formulations; biocompatibility is affirmed under ISO 10993 standards, though no full FDA approvals for PGA-based therapeutics were noted by 2025.^[40]^[43]^[44]

Food and cosmetic applications

Polyglutamic acid (PGA) serves as a versatile additive in the food industry, primarily functioning as a thickener and stabilizer to enhance texture and prevent separation in various products. In sauces and dressings, it acts as an emulsion stabilizer, improving viscosity and reducing phase separation for a smoother consistency.^[45] In baked goods such as breads and cakes, PGA increases baked volume and imparts an elastic, delicate grain structure when added at levels of 0.03-0.5% by weight, contributing to better overall texture and reduced staling.^[46] Additionally, in low-fat yogurts, it functions as a protective agent that significantly reduces syneresis—whey separation—to 23.03% (a reduction of approximately 46% relative to control) at concentrations around 0.15%.^[47] The U.S. Food and Drug Administration has recognized PGA as generally recognized as safe (GRAS) under GRN No. 339 for use in food applications, including as a de-bittering agent in salt substitutes, supporting its broad incorporation in edible products. In traditional fermented foods like natto—a Japanese soybean product—PGA occurs naturally as a sticky component produced by Bacillus subtilis during fermentation, where it contributes to potential gut health benefits by supporting intestinal microbiota balance and digestion when consumed as a dietary supplement.^[48] These benefits stem from natto's overall probiotic profile, with PGA aiding in the maintenance of healthy gut flora and reduced postprandial glucose levels in animal studies.^[49] PGA is considered edible and non-allergenic, with low concerns for adverse reactions, making it suitable for diverse dietary applications without common irritants like gluten or nuts.^[50] Its addition to food emulsions, such as dressings, can enhance shelf-life by improving stability and inhibiting microbial growth or oxidation, extending usability in processed items.^[8] In cosmetics, PGA is widely employed as a humectant in serums, creams, and moisturizers, where it attracts and retains moisture to promote skin hydration. It can hold up to 5,000 times its weight in water—approximately five times more than hyaluronic acid, which holds about 1,000 times—leading to deeper and longer-lasting hydration effects.^[51] This superior moisture-binding capacity supports anti-aging benefits by plumping the skin, reducing the appearance of fine lines through sustained hydration rather than temporary surface effects. Typically formulated at concentrations of 0.1-1% to optimize viscosity and efficacy without irritation, PGA enhances product texture while being compatible with other humectants.^[52] Since the 2010s, it has gained prominence in K-beauty products, such as hydrating serums and sheet masks from Korean brands, aligning with the trend toward multi-layered, moisture-focused skincare routines.^[53] PGA's safety profile in topical use mirrors its food-grade status, with rare allergic reactions and broad tolerability across skin types.^[54]

Environmental applications

Polyglutamic acid (PGA), particularly its γ-form, serves as an effective bioflocculant in wastewater treatment due to its anionic properties and ability to aggregate suspended particles. In applications such as palm oil mill effluent treatment, PGA at dosages around 800 ppm achieves up to 100% removal of total suspended solids (TSS), alongside 45% chemical oxygen demand (COD) reduction and 78% color removal, outperforming some conventional coagulants in efficiency and environmental compatibility.^[55] For kaolin suspensions, a flocculation rate of 95.8% is reported at 300 mg/L PGA under neutral pH conditions, demonstrating its potential to clarify water with minimal dosing. Additionally, PGA's chelating capabilities enable high-efficiency adsorption of heavy metals; Na-bonded high-molecular-weight γ-PGA removes over 98% of Pb²⁺ and 92% of Cd²⁺ from aqueous solutions at 0.5-1% concentrations and pH 7, via electrostatic interactions and complexation.^[56] In agriculture, γ-PGA acts as a soil conditioner that enhances water retention in arid and sandy soils, mitigating drought stress for crops. Application at 0.05-0.1% rates increases saturated water content by 6.3-11.5%, field capacity by 8.4-15.3%, and plant-available water by 5.1-12.5%, thereby reducing irrigation needs and stabilizing soil structure.^[57] This leads to substantial yield improvements; for winter wheat in northwest China's arid regions, γ-PGA boosts grain yield by 29.3-34.7% and water use efficiency by 21.2-33.3% compared to untreated controls.^[57] As a biodegradable carrier, γ-PGA facilitates controlled release of pesticides in nanodelivery systems, promoting plant growth while minimizing environmental leaching and enhancing bio-stimulant effects.^[58] Industrially, γ-PGA provides a sustainable alternative to synthetic polyacrylamide in processes like sugarcane juice clarification, where 0.8 ppm achieves turbidity reductions comparable to 1 ppm polyacrylamide, offering biodegradability without toxic residues.^[59] In mining operations, optimized γ-PGA formulations from Bacillus licheniformis suppress coal dust by improving wettability—reducing contact angles to near 0° within minutes—and forming adhesive films that encapsulate particles, thereby lowering airborne particulate levels through enhanced permeability and fixation.^[60] γ-PGA's environmental sustainability stems from its rapid biodegradation in soil, with approximately 61% degrading within the first day via microbial decarboxylation and mineralization, and only 26% remaining after 60 days, yielding non-toxic byproducts like glutamic acid that serve as nutrients.^[61] As a bio-based flocculant, it reduces reliance on chemical alternatives like polyacrylamide by up to 20% in dosing for equivalent performance in wastewater and industrial applications, promoting greener remediation practices.^[59]

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Several beneficial effects of poly-γ-glutamic acid (γ-PGA) have been reported. ... Hepatic lipid levels were significantly lower, the fecal bile acid and lipid ...
[27]
Factors increasing poly-γ-glutamic acid content of cheongguk-jang ...
In cheongguk-jang, bacilli are dominant bacteria and produce highly viscous poly-γ-glutamic acid (γ-PGA), which improves human health functions. The purpose of ...
[28]
Density and temperature controlled fluid extraction in a bacterial ...
Dec 17, 2022 · Polyglutamic acid is the agent that induces the fluid flux into the biofilm. We wished to identify the molecular species responsible for ...
[29]
Recent Advances in Microbial Synthesis of Poly-γ-Glutamic Acid
Mar 2, 2022 · Abstract. Poly-γ-glutamic acid (γ-PGA) is a natural, safe, non-immunogenic, biodegradable, and environmentally friendly glutamic biopolymer.
[30]
Poly (glutamic acid) – An emerging biopolymer of commercial interest
Poly (γ-glutamic acid) (PGA) is water-soluble, anionic, biodegradable, and edible biopolymer produced by Bacillus subtilis. It has multifarious potential ...
[31]
Surfactin and poly–γ–glutamic acid co–production by Bacillus ...
Optimization of γ-polyglutamic acid synthesis using response surface methodology of a newly isolated glutamate dependent Bacillus velezensis Z3. Int ...
[32]
Construction of an engineered Bacillus subtilis for production of poly ...
Sep 3, 2025 · To address this limitation, we constructed an engineered Bacillus subtilis strain by deleting hydrolase genes cwlO, pgdS and ggt, and further ...
[33]
Knockout of pgdS and ggt genes improves γ-PGA yield in B. subtilis
This study highlights the convenience of using the laboratory strain of B. subtilis over wild isolates in designing strain improvement strategies aimed at ...
[34]
Production and Characterization of Poly-γ-Glutamic Acid by Bacillus ...
Apr 16, 2025 · The strain is a glutamate-independent strain and can produce polyglutamic acid in a culture . ... cP), driving DO to 0% despite agitation ramping ...
[35]
Metabolic Engineering of Bacillus subtilis for the Production of Poly ...
Metabolic engineering aimed at improving glycerol catabolism to enhance the carbon flux towards γ-PGA in B. licheniformis resulted in up to a 70% improvement in ...
[36]
High glutamate demand enables simultaneous consumption of ...
Jun 7, 2025 · This study investigates the metabolic interplay between glycerol, citrate, and glutamate during γ-PGA synthesis, focusing on how cellular glutamate demand ...Missing: velezensis | Show results with:velezensis
[37]
Production of poly-γ-glutamic acid by glutamic acid-independent ...
The fed-batch production of γ-PGA by this strain was optimized through simultaneously and continuously feeding glucose and NH4Cl with manual and pH-stat based ...Missing: yields | Show results with:yields
[38]
https://pubmed.ncbi.nlm.nih.gov/40490120/
[39]
Peptide-targeted polyglutamic acid doxorubicin conjugates for the ...
Peptide-targeted polyglutamic acid doxorubicin conjugates for the treatment of alpha(v)beta(6)-positive cancers. Bioconjug Chem. 2008 Sep;19(9):1813-21. doi ...Missing: TLA nanoparticles
[40]
https://doi.org/10.3390/ma17010015
[41]
Poly(glutamic acid) for biomedical applications - PubMed
Paclitaxel is a widely used anti-cancer agent. Conjugates of paclitaxel with poly(glutamic acid) have shown great promise in preclinical trials.
[42]
[PDF] POLY-GAMMA-GLUTAMIC ACID
Poly-gamma-glutamic acid (γ-PGA) is a type of biopolymer that is made up of monomers of D- and/or L-glutamic acid linked together by peptide bonds. It is.Missing: nomenclature | Show results with:nomenclature
[43]
New use of polyglutamic acid for foods - Google Patents
For the production of cakes, the addition of polyglutamic acid or an edible salt in a proportion of about 0.03 to 0.5% (w/w), preferably about 0.05 to 0.3% (w/w) ...
[44]
Effects of γ-polyglutamic acid on the rheological, microstructural and ...
Mar 30, 2025 · Results: The results showed that the syneresis of low-fat yogurt added with 0.15% γ-PGA was significantly (P < 0.05) reduced to 23.03%, compared ...Missing: emulsion dressings
[45]
Effects of a high-γ-polyglutamic acid-containing natto diet on liver ...
Studies have shown that natto contains a significant quantity of γ-polyglutamic acid (γ-PGA) that is produced during the fermentation process by B. subtilis ...Results · Fecal Bile Acid Profile · Cecal Microbiota
[46]
Effects of γ-Polyglutamic Acid on Blood Glucose and Caecal Short ...
γ-Polyglutamic acid (γ-PGA) is a major component of Natto. We hypothesized that γ-PGA could reduce postprandial glucose rise and plasma glucose levels.Missing: benefits | Show results with:benefits
[47]
Polyglutamic Acid Skin Care Benefits, Uses, Side Effects - Healthline
Mar 16, 2021 · A 2015 animal study found evidence that polyglutamic may have the potential to speed up wound healing. More human research is needed to ...Benefits · Side effects · Uses
[48]
Polyglutamic Acid Benefits—and How It Compares to Hyaluronic Acid
Sep 4, 2024 · ... polyglutamic acid holds 4,000-5,000 times its weight in water. Hyaluronic acid is usually cited as 1,000 times its weight in water.” Bondi ...
[49]
What is polyglutamic acid? - Typology
Mar 2, 2022 · Polyglutamic acid may help reduce signs of aging. In addition to its moisturizing properties, relevant for preventing and reducing dehydration ...
[50]
Is Korean Skin Care Worth the Hype? Yes, and Dermatologists ...
Oct 17, 2025 · After all, K-Beauty is famous for its 10-step skin care ... Size: 1.69 | Key ingredients: Polyglutamic Acid, Ceramide, olive oil and macadamia ...
[51]
EWG Skin Deep® | What is POLYGLUTAMIC ACID
Polyglutamic Acid is a polymer of glutamic acid. It has low concerns for cancer, allergies, and developmental toxicity.Missing: allergenic | Show results with:allergenic
[52]
[PDF] Performance of Polyglutamic Acid in Palm Oil Mill Effluent Treatment
Mar 12, 2020 · It found that the optimum pH and dosage of PGA in POME for COD, color, and. TSS removal are at pH 3 and 800 ppm. Findings revealed with this ...
[53]
Effective Removal of Different Heavy Metals Ion (Cu, Pb, and Cd ...
It was found that Na-bonded γ-PGA with a high molecular weight showed the highest heavy metal adsorption (92.2–98.3%), particularly at a 0.5% concentration ...
[54]
Poly-γ-glutamic acid enhances the wheat yield, water use efficiency ...
The results indicated that γ-PGA significantly increased saturated water content by 6.3-11.5%, field capacity by 8.4-15.3%, and plant available water by 5.1- ...
[55]
Bio-stimulant based nanodelivery system for pesticides with high ...
Jul 1, 2024 · A bio-stimulant based nanocarrier for pesticide delivery has been fabricated. The nanocarrier promotes the growth of plant.
[56]
Poly‐γ‐glutamic acid produced from Bacillus licheniformis CGMCC ...
May 29, 2015 · Poly-γ-glutamic acid produced from Bacillus licheniformis CGMCC 2876 as a potential substitute for polyacrylamide in the sugarcane industry.
[57]
Optimized biosynthesis and performance enhancement of γ-PGA ...
Jul 7, 2025 · This study utilized response surface methodology to optimize the conditions for microbial fermentation to synthesize the biobased dust suppressant γ-PGA.
[58]
Effects of poly-γ-glutamic acid (γ-PGA) on plant growth and its ...
Jul 20, 2017 · γ-PGA significantly improved plant uptake of nitrogen (N), phosphorus (P), and potassium (K) and hence increased plant biomass.