Biological Activity of Microbial Melanin
Study of Biological Activity of Microbial Water-Soluble Melanin as a Phytostimulator and Prospective Pharmacological Agent. Construction of New Active Melanin Producing Strains
Tech Area / Field
- BIO-IND/Industrial Biotechnology/Biotechnology
- MED-DRG/Drug Discovery/Medicine
3 Approved without Funding
Scientific and Production Center "Armbiotechnology" NAS RA, Armenia, Yerevan
- Yerevan State University, Armenia, Yerevan
- University of Toronto / Faculty of Pharmacy, Canada, ON, Toronto\nIstituto di Chimica Biomolecolare/Consiglio Nazionale delle Ricerche (ICB-CNR), Italy, Napoli\nOhio State University / Health Sciences Center, USA, OH, Columbus\nFraunhofer USA - Center for Molecular Biotechnology, USA, DE, Newark
Project summaryMelanins, pigments of polymer structure, are known to be unique energy transmitters. Being amorphous semiconductors, they are able to absorb and scatter various types of energy. Disturbances of melanin metabolism are involved in the etiology of various disorders, such as Parkinsonism, senile deafness, pigment anomalies, Vaardenburg's, Usher's and Down's syndromes, Alzheimer disease, etc. Melanins are used in the pharmacology and cosmetics as antioxidants, radioprotectors, preparations against ageing diseases and for skin and eye protection from UV-irradiation. Melanin photoprotective, immunostimulating and mitogen activities are investigated actively. Melanins are applied as an ingredient of sunscreens. At the same time there are obstacles to apply melanins in the practice. Production of synthetic melanins is expensive; as to of natural melanins derived from different sources, their features are very various. The most melanins are water-insoluble that interferes with the preparation of melanin-containing products.
In 2002-2004 we implemented the ISTC Project A-683. Mutant strains of Bacillus thuringiensis possessing the high level of bacterial melanin (BM) synthesis were isolated. The technology of BM production and purification were developed. The main physicochemical features of BM were studied; its ecological safety was demonstrated. The BM produced was shown to be an amorphous high-molecular water-soluble polymer, deep-brown colored pigment. Its cost, according to prior calculation, is lower in tens times than the price of synthetic melanins or pigments prepared from other sources. Investigation of BM features performed in the frames of the Project A-683 has revealed its high biological activity. BM was shown to be mighty phytostimulator with hormone-like effect on plant growth and development both in vivo and in vitro. In experiments on laboratory animals with brain surgical trauma BM promoted the recovery of physiological functions and brain tissue regeneration. Preliminary experiments on vertebrate cell cultures revealed that BM was not toxic for cells at concentrations many times higher than physiological ones and that cancer cells were more sensitive to the toxic effect of BM high concentrations than normal cells.
The objective of this proposed Project having fundamental and applied value and developing of achievements of the Project A-683 is the study of BM biological activity as phytostimulator and potential pharmacological agent, the improvement of BM quality and perfection of technology of BM production.
Researchers from the Institute of Biotechnology and Yerevan State University (Yerevan, Armenia) will participate in the Project. They have essential experience in joint work and in performance of international research programs. Project participants are highly qualified experts in genetics, biotechnology, cell biology, plant physiology and toxicology. The research teams involve 7 Doctors of Sciences and 21 Candidates of Sciences (Ph.D.).
The proposed Project implementation will exert long-term influence on further investigations of various melanins as biologically active substances. Technologically efficient production of cheap water-soluble natural melanin and description of its biological activities will throw this valuable product available for common usage in pharmacology, cosmetology, agriculture and other areas and ensure the future commercial success of this Project. The study of BM effects will open for the Project participants a long-term prospective to develop new active preparations including BM.
The Project proposed fully meets the ISTC goals and promotes them to be realized.
In the frames of this Project the main biological effects of BM will be studied (the antioxidant and radioprotective activity, the ability to protect cells from UV-irradiation and heat shock, the mitogenic and motogenic activities, the influence on the organism immune status, effects on cancer cells). The recommendations on BM application as pharmacological and cosmetic preparation will be developed. On test-systems in vivo (laboratory animals) and in vitro (cell cultures) the acute and chronic toxicity, cyto- and genotoxicity of BM will be analyzed. The study of BM as a stimulator of the plant growth and development in vivo and in vitro will be continued. The recommendations on the BM application in the agriculture and plant biotechnology will be prepared. The influence of BM on reparative processes in damaged central and peripheral nervous systems and at the immobilization stress will be investigated. It is planned to construct new strains of microorganisms producing BM to develop profitable production of BM and bring the product features in full correspondence with demands of pharmacological industry. The recommendations on BM production will be prepared.
In the process of the Project implementation the participants and collaborators will continuously change the information on work progress results obtained, etc. The collaborators will comment interim and final reports presented to ISTC, will carry out cross-examination of results and technical examination of participant activity. Joint experiments will be performed using collaborators’ equipment. Joint workshops will be organized periodically.
In the process of the Project implementation a number of techniques will be applied: methods of animal and plant cell culture and testing in vitro; field investigation of plants; analysis of plant enzyme activity; study of morphology and function of nervous system; techniques of genetic engineering and microorganism biotechnology; determination of toxicity and genotoxisity in vivo and in vitro.