polyglutamic acid
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| ImageCaption = Gamma PGA
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| SystematicName = Poly[imino[1-carboxy-4-oxo-1,4-butanediyl]]
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| CASNo = 25736-27-0
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| Formula = (C5H7NO3)n
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Polyglutamic acid (PGA) is a polymer of the amino acid glutamic acid (GA). Depending on where the individual monomers connect, PGA can be gamma PGA (poly-γ-glutamic acid, γ-PGA), the form where the peptide bonds are between the amino group of GA and the carboxyl group at the end of the GA side chain, or alpha PGA, the form where the alpha-carboxyl is used to form the peptide bond.
Gamma PGA is formed by bacterial fermentation. It is a major constituent of the Japanese food nattō and has a wide range of uses.
Alpha PGA has been investigated as a drug delivery system.
Structure
Both form of PGA are linked together by peptide bonds. Because the glutamic acid has a chiral center, both forms of PGA can be made from L-glutamic acid, D-glutamic acid, or a mixture of both. In practical use, alpha PGA is composed mostly of L-glutamic acid,{{cite journal |last1=Zhang |first1=Y |last2=Song |first2=W |last3=Lu |first3=Y |last4=Xu |first4=Y |last5=Wang |first5=C |last6=Yu |first6=DG |last7=Kim |first7=I |title=Recent Advances in Poly(α-L-glutamic acid)-Based Nanomaterials for Drug Delivery. |journal=Biomolecules |date=25 April 2022 |volume=12 |issue=5 |page=636 |doi=10.3390/biom12050636 |pmid=35625562 |pmc=9138577 |doi-access=free }} while gamma PGA tends to have a mixture of both.{{cite journal |last1=Li |first1=D |last2=Hou |first2=L |last3=Gao |first3=Y |last4=Tian |first4=Z |last5=Fan |first5=B |last6=Wang |first6=F |last7=Li |first7=S |title=Recent Advances in Microbial Synthesis of Poly-γ-Glutamic Acid: A Review. |journal=Foods |date=2 March 2022 |volume=11 |issue=5 |doi=10.3390/foods11050739 |pmid=35267372 |pmc=8909396 |doi-access=free }}
Properties
Gamma PGA is non-immunogenic and biodegradable. It hydrolyzes in hot water.{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/27286372/ | pmid=27286372 | date=1992 | last1=Goto | first1=A. | last2=Kunioka | first2=M. | title=Biosynthesis and Hydrolysis of Poly(γ-glutamic acid) from Bacillus subtilis IF03335 | journal=Bioscience, Biotechnology, and Biochemistry | volume=56 | issue=7 | pages=1031–1035 | doi=10.1271/bbb.56.1031 | doi-access=free }}
Both forms are amphiphilic, water-soluble, and have a negative charge.
Synthesis
Gamma PGA is industrially made by fermentation. The biosynthetic process starts with racemerization by RacE, which converts L-glutamate to D-glutamate. A set of genes on an operon then proceed to assemble the molecule and move it out of the bacterial cell.
Alpha PGA is industrially made by chemical synthesis, using a ring-opening polymerization reaction.
Occurrence
Gamma PGA is made by a number of Bacillus species. The best-known source is natto, where it is produced by Bacillus subtilis.{{cite journal |last1=Johnson |first1=Leah C. |last2=Akinmola |first2=Adekunle Titus |last3=Scholz |first3=Carmen |title=Poly(glutamic acid): From natto to drug delivery systems |journal=Biocatalysis and Agricultural Biotechnology |date=March 2022 |volume=40 |pages=102292 |doi=10.1016/j.bcab.2022.102292|s2cid=246628249 }} It is also an important component of the Bacillus anthracis capsule, hiding the bacterium from the immune system and allowing it to grow unchecked.{{cite journal |last1=Jang |first1=J |last2=Cho |first2=M |last3=Chun |first3=JH |last4=Cho |first4=MH |last5=Park |first5=J |last6=Oh |first6=HB |last7=Yoo |first7=CK |last8=Rhie |first8=GE |title=The poly-γ-D-glutamic acid capsule of Bacillus anthracis enhances lethal toxin activity. |journal=Infection and Immunity |date=September 2011 |volume=79 |issue=9 |pages=3846–54 |doi=10.1128/IAI.01145-10 |pmid=21690241|pmc=3165481 }}
Uses
Gamma PGA has been used for food (potential thickener), medicine (pre-clinical),{{Cite journal |last1=Choi |first1=Jae-Chul |last2=Uyama |first2=Hiroshi |last3=Sung |first3=Chul-Hoon Lee and Moon-Hee |date=2015-06-28 |title=Promotion Effects of Ultra-High Molecular Weight Poly-γ-Glutamic Acid on Wound Healing |journal=Journal of Microbiology and Biotechnology |language=en |volume=25 |issue=6 |pages=941–945 |doi=10.4014/jmb.1412.12083|pmid=25791849 |doi-access=free }}{{Cite journal |last1=Lee |first1=Na-Ri |last2=Go |first2=Tae-Hun |last3=Lee |first3=Sang-Mee |last4=Jeong |first4=Seong-Yun |last5=Park |first5=Geun-Tae |last6=Hong |first6=Chang-Oh |last7=Son |first7=Hong-Joo |date=2014-04-21 |title=In vitro evaluation of new functional properties of poly-γ-glutamic acid produced by Bacillus subtilis D7 |journal=Saudi Journal of Biological Sciences |volume=21 |issue=2 |pages=153–158 |doi=10.1016/j.sjbs.2013.09.004 |issn=1319-562X |pmc=3942858 |pmid=24600308}} cosmeceuticals{{Cite web |last=Eroglu |first=I. |date=March 12, 2022 |title=Polyglutamic Acid in Skincare, Explained |url=https://www.ejollify.com/polyglutamic-acid/ |access-date=April 12, 2022 |website=Ejollify}} and water treatment.[https://www.japan.go.jp/tomodachi/2016/g7-2016/contributing3.html Bringing Safe Drinking Water to the World]
Alpha PGA is used as a delivery aid for paclitaxel, an anticancer drug,{{cite journal |author1=C. Li |author2=D.F. Yu |author3=A. Newman |author4=F. Cabral |author5=C. Stephens |author6=N.R. Hunter |author7=L. Milas |author8=S. Wallace | journal = Cancer Research | volume = 58 | year = 1998 | pages = 2404–2409 | pmid = 9622081 |url=https://cancerres.aacrjournals.org/content/canres/58/11/2404.full.pdf | title = Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate | issue = 11}} under the generic name of paclitaxel poliglumex.{{cite journal |last1=Singer |first1=JW |title=Paclitaxel poliglumex (XYOTAX, CT-2103): a macromolecular taxane. |journal=Journal of Controlled Release |date=5 December 2005 |volume=109 |issue=1–3 |pages=120–6 |doi=10.1016/j.jconrel.2005.09.033 |pmid=16297482}} Research is underway for its application in a treatment of type I diabetes and its potential use in the production of an AIDS vaccine.{{Citation needed|date=January 2018}}
= Water treatment =
The "PolyGlu PGα21Ca" water flocculant, based on a mixture of gamma PGA, calcium sulfate, and calcium carbonate,{{cite journal |last1=Yanagibashi |first1=Tomokazu |last2=Kobayashi |first2=Motoyoshi |last3=Omori |first3=Keisuke |title=Application of Poly-γ-Glutamic Acid Flocculant to Flocculation–Sedimentation Treatment of Ultrafine Cement Suspension |journal=Water |date=22 August 2019 |volume=11 |issue=9 |pages=1748 |doi=10.3390/w11091748 |quote=A food-derived amino acid-based polymer, namely the PGAF (PGα21Ca, Japan Poly-Glu Co., Ltd., Osaka, Japan), was used as the flocculant. Figure 3 shows the appearance of PGα21Ca. PGα21Ca is a natural polymer consisting of γ-PGA, which is an amino acid obtained from Bacillus subtilis [7]. PGα21Ca is composed of cross-linked γ-PGA with an average molecular weight of 107 and natural minerals such as calcium sulfate and calcium carbonate hydrate. |doi-access=free }} is used by the International Organization for Migration to treat water for refugees.{{cite web |title=UN Migration Agency, Japan Hand Over New Water Purification Facility in Sierra Leone |url=https://www.iom.int/news/un-migration-agency-japan-hand-over-new-water-purification-facility-sierra-leone |website=International Organization for Migration |language=en}}
G-PGA covalently incorporated into microfiltration membranes via attachment to their membrane pore surfaces exhibited super-high heavy metal sorption ability.{{cite journal |last1=Bhattacharyya |first1=D |title=Novel poly-glutamic acid functionalized microfiltration membranes for sorption of heavy metals at high capacity |journal=Journal of Membrane Science |date=April 1998 |volume=141 |issue=1 |pages=121–135 |doi=10.1016/S0376-7388(97)00301-3}}
G-PGA was found to bind and efficiently remove 99.8% of lead ions from water via a suitable low-pressure ultrafiltration technique.Inbaraj et al. (2006){{Full citation needed|date=September 2023}}