Polylysine refers to several types of

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

homopolymers, which may differ from each other in terms of stereochemistry (D/L; the L form is natural and usually assumed) and link position (α/ε). Of these types, only ε-poly-L-lysine is produced naturally.

Chemical structure

The precursor

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

lysine contains two

amino group In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

s, one at the

α-carbon In the nomenclature of organic chemistry, a locant is a term to indicate the position of a functional group or substituent within a molecule. Numeric locants The International Union of Pure and Applied Chemistry (IUPAC) recommends the use of n ...

and one at the ε-carbon. Either can be the location of

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...

, resulting in α-polylysine or ε-polylysine. Polylysine is a homopolypeptide belonging to the group of

cationic An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

polymer A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...

s: at pH 7, polylysine contains a positively charged

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

amino group. Alpha-Polylysine

α-Polylysine is a synthetic polymer, which can be composed of either L-lysine or D-lysine. "L" and "D" refer to the

chirality Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable fro ...

at lysine's central carbon. This results in poly-L-lysine (PLL) and poly-D-lysine (PDL) respectively. ε-Polylysine (ε-poly-L-lysine, EPL) is typically produced as a homopolypeptide of approximately 25–30 L-lysine residues. According to research, ε-polylysine is adsorbed electrostatically to the cell surface of the bacteria, followed by a stripping of the outer membrane. This eventually leads to the abnormal distribution of the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

causing damage to the bacterial cell that is produced by bacterial fermentation. ε-Poly-L-lysine is used as a natural preservative in food products.

Production

Production of polylysine by natural fermentation is only observed in strains of bacteria in the genus ''

Streptomyces ''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

''. '' Streptomyces albulus'' is most often used in scientific studies and is also used for the commercial production of ε-polylysine. α-Polylysine is synthetically produced by a basic

polycondensation In polymer chemistry, condensation polymers are any kind of polymers whose process of polymerization involves a condensation reaction (i.e. a small molecule, such as water or methanol, is produced as a byproduct). Natural proteins as well as s ...

reaction.

History

The production of ε-polylysine by natural fermentation was first described by researchers Shoji Shima and Heiichi Sakai in 1977. Since the late 1980s, ε-polylysine has been approved by the Japanese

Ministry of Health, Labour and Welfare The is a cabinet level ministry of the Japanese government. It is commonly known as in Japan. The ministry provides services on health, labour and welfare. It was formed with the merger of the former Ministry of Health and Welfare or and th ...

as a preservative in food. In January 2004, ε-polylysine became

generally recognized as safe Generally recognized as safe (GRAS) is a United States Food and Drug Administration (FDA) designation that a chemical or substance added to food is considered safe by experts under the conditions of its intended use. An ingredient with a GRAS d ...

(GRAS) certified in the United States.GRAS Notice No. GRN 000135

ε-Polylysine

In food

ε-Polylysine is used commercially as a food

preservative A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or ...

in Japan, Korea and in imported items sold in the United States. Food products containing polylysine are mainly found in Japan. The use of polylysine is common in food applications such as boiled rice, cooked vegetables, soups,

noodles Noodles are a type of food made from unleavened dough which is either rolled flat and cut, stretched, or extruded, into long strips or strings. Noodles are a staple food in many cultures and made into a variety of shapes. The most common noo ...

and sliced fish (

sushi is a traditional Japanese dish made with , typically seasoned with sugar and salt, and combined with a variety of , such as seafood, vegetables, or meat: raw seafood is the most common, although some may be cooked. While sushi comes in n ...

). Literature studies have reported an

antimicrobial An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth (bacteriostatic agent). Antimicrobial medicines can be grouped according to the microorganisms they are used to treat. For example, antibiotics are used aga ...

effect of ε-polylysine against

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain ...

and

Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

. Polylysine has a light yellow appearance and is slightly bitter in taste whether in powder or liquid form.

α-Polylysine

In tissue culture

α-Polylysine is commonly used to coat tissue cultureware as an attachment factor which improves cell adherence. This phenomenon is based on the interaction between the positively charged polymer and negatively charged cells or proteins. While the poly-L-lysine (PLL) precursor amino acid occurs naturally, the poly-D-lysine (PDL) precursor is an artificial product. The latter is therefore thought to be resistant to enzymatic degradation and so may prolong cell adherence.

Polylysine in drug delivery

Polylysine exhibits high positive charge density which allows it to form soluble complexes with negatively charged

macromolecule A macromolecule is a "molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass." Polymers are physi ...

s. Polylysine homopolymers or block copolymers have been widely used for delivery of DNA and proteins. Polylysine-based

nanoparticle A nanoparticle or ultrafine particle is a particle of matter 1 to 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 100 nm in only two directions. At ...

s have also been shown to passively accumulate in the injured sites of

blood vessels Blood vessels are the tubular structures of a circulatory system that transport blood throughout many animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste an ...

after

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

due to incorporation into newly formed

thrombus A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...

, which offers a new way to deliver therapeutic agents specifically to the sites of injury after vascular damage.

Chemical modification

In 2010, hydrophobically modified ε-polylysine was synthesized by reacting EPL with octenyl succinic anhydride (OSA).Yu, et al, J. Agri Food Chem, 2010 Jan 27;58(2):1290-5. It was found that OSA-g-EPLs had

glass transition The glass–liquid transition, or glass transition, is the gradual and Reversible reaction, reversible transition in amorphous solid, amorphous materials (or in amorphous regions within Crystallinity, semicrystalline materials) from a hard and rel ...

temperatures lower than EPL. They were able to form polymer micelles in water and to lower the surface tension of water, confirming their amphiphilic properties. The antimicrobial activities of OSA-g-EPLs were also examined, and the minimum inhibitory concentrations of OSA-g-EPLs against ''Escherichia coli'' O157:H7 remained the same as that of EPL. Therefore, modified EPLs have the potential of becoming bifunctional molecules, which can be used either as surfactants or emulsifiers in the encapsulation of water-insoluble drugs or as antimicrobial agents.

References

{{reflist Food additives Food preservatives Polymers Amino acid derivatives