Gene screening of actinomycetes producing new substances with potential therapeutic applications to modulate immune mechanisms.
Project goals
The project aims to acquire new secondary metabolites of the manumycin type from soil-isolated actinomycetes. These non-steroidal compounds show interesting immunomodulatory features (IL-1ß convertase inhibition) that could potentially be used in treatment of inflammation. Based on our knowledge on the function of gene essential for their biosynthesis, we have designed a method of the specific genetic screening to identify new production strains, which has already been tested with a set of model and non-characterized strains. In the course of the project new actinomycete strains will be isolated from suitable soil biotopes and potential producers of the manumycin metabolites will be selected by genetic screening. Positive strains will be further characterised and their secondary metabolites production will be analysed. The structure of acquired compounds will be identified and their biological activity assayed, concentrating on the antiinflammatory and immunomodulatory features.
Keywords
gene screeningactinomycetessecondary metabolitesbiotechnology of production strainsmanumycin-type antibioticsantiinflammatory and immunomodulatory compoundsmolecular cloninginterleukin IL-1ßcaspase 1 inhibition
Public support
Provider
Academy of Sciences of the Czech Republic
Programme
Grants of distinctly investigative character focused on the sphere of research pursued at present particularly in the Academy of Sciences of the Czech Republic
Call for proposals
Výzkumné granty 6 (SAV02006-A)
Main participants
—
Contest type
VS - Public tender
Contract ID
IAA600660607
Alternative language
Project name in Czech
Vyhledávání (genový "screening") aktinomycet produkujících nové látky s potenciálním terapeutickým využitím k zásahu do imunitních mechanismů
Annotation in Czech
Projekt je zaměřen na získání nových sekundárních metabolitů ze skupiny manumycinových antibiotik z půdních izolátů aktinomycet. Tyto nesteroidní látky vykazují zajímavé imunomodulační vlastnosti (zejména inhibici konvertasy IL-1ß), které jsou potenciálně využitelné při léčbě zánětu. Na základě znalosti funkce genů, esenciálních pro syntézu těchto látek, jsme navrhli a na vzorku modelových i necharakterizovaných kmenů otestovali metodu specifického genového "screeningu" pro identifikaci nových produkčních kmenů tohoto typu látek. V průběhu projektu budou z vhodných půdních biotopů izolovány nové kmeny aktinomycet a genovým "screeningem" z nich budou vybráni potenciální producenti manumycinových látek. Pozitivní kmeny budou dále charakterizovány a budeanalyzováno spektrum jimi syntetizovaných sekundárních metabolitů. U získaných látek bude určena chemická struktura a ověřeny jejich biologické účinky, se zaměřením na inhibici zánětlivých procesů a imunomodulaci.
Scientific branches
R&D category
ZV - Basic research
CEP classification - main branch
EE - Microbiology, virology
CEP - secondary branch
EI - Biotechnology and bionics
CEP - another secondary branch
EH - Ecology - communities
10606 - Microbiology
10607 - Virology
10618 - Ecology
10619 - Biodiversity conservation
20801 - Environmental biotechnology
20802 - Bioremediation, diagnostic biotechnologies (DNA chips and biosensing devices) in environmental management
20803 - Environmental biotechnology related ethics
20901 - Industrial biotechnology
20902 - Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation
20903 - Bioproducts (products that are manufactured using biological material as feedstock) biomaterials, bioplastics, biofuels, bioderived bulk and fine chemicals, bio-derived novel materials
30401 - Health-related biotechnology
30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)
30403 - Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions [pharmacogenomics, gene-based therapeutics])
30404 - Biomaterials (as related to medical implants, devices, sensors)
30405 - Medical biotechnology related ethics
40401 - Agricultural biotechnology and food biotechnology
40402 - GM technology (crops and livestock), livestock cloning, marker assisted selection, diagnostics (DNA chips and biosensing devices for the early/accurate detection of diseases) biomass feedstock production technologies, biopharming
40403 - Agricultural biotechnology related ethics
Completed project evaluation
Provider evaluation
U - Uspěl podle zadání (s publikovanými či patentovanými výsledky atd.)
Project results evaluation
There were discovered 13 soil streptomycete strains - potential producers of manumycine type of antibiotics. New manumycin antibiotics, asukamycin H and I, were isolated from the geneticaly manipulated streptomycete strain with the help of metabolic engin
Solution timeline
Realization period - beginning
Jan 1, 2006
Realization period - end
Dec 31, 2008
Project status
U - Finished project
Latest support payment
Feb 21, 2008
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP09-AV0-IA-U/01:1
Data delivery date
Jul 2, 2009
Finance
Total approved costs
4,337 thou. CZK
Public financial support
4,337 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK
Basic information
Recognised costs
4 337 CZK thou.
Public support
4 337 CZK thou.
100%
Provider
Academy of Sciences of the Czech Republic
CEP
EE - Microbiology, virology
Solution period
01. 01. 2006 - 31. 12. 2008