Pyomelanin

Pyomelanin

Homogentisic acid (monomere form of Pyomelanin)

Names
IUPAC name 2,5-Dihydroxyphenylacetic acid
Identifiers
CAS Number	451-13-8 Y
ChemSpider	759 Y
PubChem CID	780
Properties
Chemical formula	C8H8O4
Molar mass	168.148 g·mol−1
Melting point	150 to 152 °C (302 to 306 °F; 423 to 425 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Pyomelanin is one of the five basic types of melanin. It is a polymer resulting from the oxidation and polymerization of Homogentisic acid ( HGA ).

Differents forms of possible polymerization of HGA into Pyomelanin

This brownish pigment can be produced by microorganisms like bacterias and fungus.

It has several properties such as metal bonding, redox and electron shuttle, and protective roles such as anti-microbial activity or anti-oxidative stress. These properties are mainly used in cosmetics and pharmacology.

Historical context

Pyomelanin was first discovered in 1897 by a French cavalryman. This molecule was reported as a “pyocyanic bacillus”by Maxime Radais at the Faculty of Pharmacy in Paris. To cure a rare disease, the alkaptonuria (ALK) that appeared in 1902, researches led to rediscover the “pyocyanic bacillus”, that was then reevaluated and validated as pyomelanin.

Synthesis

Natural Synthesis

In opposition to other types of melanin, pyomelanin is a molecule synthesized in the human body in specific cases, by microorganisms such as bacteria and fungi. This molecule can be produced in certain pathological conditions, or in response to environmental stress.

Its production is encouraged by a tyrosine-enriched environment. The latter results from an enzyme deficiency that leads to an accumulation of homogentisic acid (HGA), produced by 26 genes, which can cause a genetic disease : alkaptonuria. In this case, the excessive production of pyomelanin can lead to ochronosis, dark colouration of the urine, unusual pigmentation of the skin and degradation of the skin cartilage (arthritis).

In a healthy body, the production of pyomelanin is therefore blocked by the enzyme homogentisate 1,2-dioxygenase which prevents the accumulation of HGA.

Artificial Synthesis

The artificial synthesis of the polymer, Pyomelanin, always starts with L-Tyrosine. Then mimic the natural way by transforming L-Tyrosine to the Homogentisic acid (HGA) using Laccase. Then HGA oxidizes and polymerizes into Pyomelanin.

This procedure starts from 2,5-Depot Medroxyprogesterone acetate (2,5-DMPA) and HGA-Lactone is the most convenient one due to its three-step successive process, others procedures exist but are not used as much (due to the cost of reactifs and complexity of the reactions).

Properties

DPPH-Antioxidant Activity

Pyomelanin possesses antioxidant activity, as evidenced by its interaction with DPPH (2,2-Diphenyl-1-picrylhydrazyl). When pyomelanin is tested with the latter, it can reduce the stable DPPH radical to its non-radical form, leading to a decrease in absorbance, which indicates a strong free radical scavenging activity. Pyomelanin could play a role in protecting biological systems against oxidative stress.

Electron Transfer and Fe³⁺ -Reducing activities

Due to its redox properties, pyomelanin plays a role in electron transfer and Fe³⁺ reduction to Fe²⁺. It can act as a terminal electron acceptor, an electron shuttle, or a conduit facilitating electron transport. This property enhances the current response of biofilms, particularly in microbial fuel cells, thereby promoting electricity production. Additionally, pyomelanin contributes to the mobilization and storage of cations in the environment. In its reduced form, it can anaerobically reduce Fe³⁺ to Fe²⁺, a crucial process for maintaining cellular homeostasis, especially in organisms lacking transporters or siderophores. In Legionella pneumophila, both Homogentisic acid (HGA) and pyomelanin facilitate Fe³⁺ reduction, making Fe²⁺ available for bacterial uptake. Furthermore, under low dissolved oxygen levels, the HGA pigment accelerates solid-phase metal reduction, aiding in the survival of bacteria such as Shewanella oneidensis MR-1.

A moderate Anti-Inflammatory Activity

The effect of Pyomelanin on inflammation is primarily based on its ability to reduce reactive oxygen species (ROS), which play a role in inflammatory processes. A study on the pseudoalteromonas lipolytica BTCZ28 strain successfully isolated pyomelanin in the form of ultra-small Pyomelanin nanogranules (PNG) and evaluated its anti-inflammatory activity. Tests conducted on LPS-activated murine macrophages (RAW 264.7) showed a moderate reduction in NO radical production by approximately 30% at a concentration of 100 µg/mL of PNG. Analysis of the cell lysate from this strain revealed significant inhibition of several inflammatory enzymes: cyclooxygenase (IC₅₀ = 95.5 µg/mL), lipoxygenase (IC₅₀ = 88.9 µg/mL), and myeloperoxidase (a fivefold decrease in activity at 100 µg/mL). These findings suggest that Pyomelanin could be used in therapeutic applications to modulate inflammation.

Against oxidative stress

Pyomelanin has protective properties against oxidative stress. Research has shown that a hppD gene (4-hydroxyphenylpyruvate dioxygenase), and a low expression of the hppA gene (homogentisa dioxygenase), results in high production of homogentisic acid (HGA) which then oxidizes to form Pyomelanin in microorganizations . Furthermore, the inactivation of the hppA gene reduces bacterial tolerance to oxidative stress caused by environmental aggressions . These studies thus confirm the essential role of Pyomelanin in protecting bacteria.

Antimicrobial activity

Many micro - organisms are capable of producing Pyomelanin in their strains, and for some, the production of increasing quantities of Pyomelanin makes some of their strains aggressive, and this overproduction of pyomelanin disrupts the homogentisate oxidase (HGO) . This hyperproduction promotes better adaptation to chronic infections. Research has been carried out on this important property of Pyomelanin against antimicrobial activities

UV free radicals

Pyomelanin protects micro-organisms against ultraviolet radiation, reducing the formation of free radicals and increasing their resistance to light. Studies have been carried out on this property of Pyomelanin, in particular against ultraviolet A (UVA) radiation, known to induce reactive oxygen species (ROS), which generate free radicals that can lead to collagen cross-linking and degradation. This research has confirmed the anti-free radical role of Pyomelanin in the face of harmful radiation.