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New type of natural melanin: basic studies and production technology

#A-683


Investigation of a new type of water soluble natural biologically active melanin: development of the technology for biosynthesis: extraction and purification; study of the chemical structure, physiological activity

Tech Area / Field

  • BIO-CHM/Biochemistry/Biotechnology
  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • BIO-MIB/Microbiology/Biotechnology
  • CHE-POL/Polymer Chemistry/Chemistry
  • BIO-IND/Industrial Biotechnology/Biotechnology
  • MED-DRG/Drug Discovery/Medicine

Status
8 Project completed

Registration date
12.02.2001

Completion date
21.10.2005

Senior Project Manager
Weaver L M

Leading Institute
Institute of Biotechnology, Armenia, Yerevan

Supporting institutes

  • L.A.Orbeli Institute of Physiology, Armenia, Yerevan

Collaborators

  • University of South Carolina / Department Civil & Environmental Engineering, USA, CA, Los-Angeles\nFraunhofer USA - Center for Molecular Biotechnology, USA, DE, Newark

Project summary

The purpose of the Project is to a) study and develop the technology of biosynthesis, extraction and purification of a new water-soluble natural biologically active melanin, produced by a mutant strain of Bacillus thuringiensis (BT); b) to study its physiological activity, chemical structure and possible synthesis of new biologically active substances and melanin-based pharmacological compounds.
Therefore, the proposed project is to be the first attempt to conduct complex investigations involving the elaboration of technology of this group of melanins, resulting in obtaining purified substances; economic and marketing problems; basic research revealing the chemical structure and, especially, their biological activity, both for eukaryotic and prokaryotic systems.
The problems connected with the production of melanin and melanin-like pigments and their practical use still remain urgent and prospective, not only for researchers in medicine, biology, chemistry, biotechnology, toxicology, etc., but also for their consumers: pharmacists, cosmetologists, treating physicians, etc. The enormous volume of scientific publications and patent literature, which is devoted to melanin, illustrates this fact, so we can see that the need for these substances will grow from year to year.
Melanin extracted from microorganisms, micromycetes, fungi and dark grapes, shows similar properties with melanin of animal origin. They are pharmacologically active substances with anti-oxidizing, anti-toxic, anti-inflammatory, antitumor, bioprotective and immunostimulating properties that offer protection from photodynamic damages, etc.
The application of melanin is limited because of the difficulty of extraction, purification of albumin impurity and technological expense. They are mainly used as an active component of photoprotective ointments and creams. Therefore, the proposed project is aimed at cheaper production of biologically active melanin and melanin-based substances.
The present project is based on the earlier described BT melanogenic strain, which produces water-soluble dark-brown melanin. Melanogenesis of this strain is conditioned by mutation in the biochemical pathway of L-tyrosine utilization, i.e. activity of the homogentisate-dioxygenase enzyme that catalyzes oxidation of one of the intermediate substances – homogentisic acid in 4-maleylacetoacetic acid has been lost. And, though similar melanogenesis has been known to specialists since the end of the XIX century, the properties, chemical structure and biological activities of these melanins have been barely investigated.
Recently, the authors have performed interim studies of the biological activity of BT-produced melanin. High biological activity of plants was observed. The anatomical investigations of BT melanin-treated plants have revealed that increased growth and fruit ripening correlate to their cambial activities and promote better development of vascular tissue of xilom and phloem. This phenomenon makes more intensive the inflows of water with mineral elements from roots and photosynthesis products from leaves.
These results dictate the need for a continuation of basic research, not only in the field of biological activity of BT melanin, but also of its chemical nature and molecular structure. They also show the importance of applied investigations in biosynthesis of melanin itself, its extraction and purification. The advantage of the proposed method for the synthesis of biologically active BT melanin consists in the fact that the producing strain is an industrial microorganism and is used for production of biological insecticides that should supply the most profitable technological process for producing purified BT melanin with less expense.
So, main tasks to be solved:
1. Development of technology for BT melanin biosynthesis, extraction and purification.
2. Study of BT melanin chemical structure and physico-chemical properties.
3. Study of BT melanin biological activity in plants and cell cultures.
4. Study of BT melanin biological activity in humans and animals
Two technical documents will be issued:

a) for production of new natural biologically active water-soluble melanin;
b) for production of bacterial insecticide using melanogenic strain of BT.

Upon completion of the corresponding research, the patenting of the following objects is assumed:
- melanin strain-producer;
- process for melanin production;
- process for bacterial insecticide production;
- water-soluble biologically active natural melanin.
Technological development will be applied on pilot-scale facilities at the Institute of Biotechnology, using industrial-scale quantities of raw materials, followed by waste treatment and utilization. The high cost of the present Project is reasonable and accounted for by the performance of this technologically complicated semi-industrial process. Realization of the present Project will also correspond with the aims and goals of the ISTC.


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