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Expression of lincomycin biosynthetic gene cluster and its regulation

Project goals

The project aims in finding the organization of transcriptional units within the lincomycin biosynthetic cluster and identifying transcription starts. Based on previous results, e.g. the known sequence of the lincomycin biosynthetic gene cluster and partial knowledge of its pathway, putative regulatory genes were proposed. Functions of the proposed genes will be elucidated by inactivation and increasing the gene dose, respectively. The impact on lincomycin production will be observed. Preparation ofa cosmid library, gene inactivation, localization of transcription starts (primer extension), cDNA preparation and hybridization (microarray) will compose the methodical approach employed in the project. Determination of regulatory genes within the lincomycin biosynthetic cluster and their interference in expresion of individual genes and resulting antibiotic production are the expected results. Information on pathway-specific regulators and organization of transcription units is indispensable for

Keywords

Streptomyces lincolnensislincomycinpathway-specific regulators

Public support

  • Provider

    Czech Science Foundation

  • Programme

    Standard projects

  • Call for proposals

    Standardní projekty 8 (SGA02005GA-ST)

  • Main participants

  • Contest type

    VS - Public tender

  • Contract ID

    204/05/0616

Alternative language

  • Project name in Czech

    Exprese genů biosyntetického shluku linkomycinu a její regulace

  • Annotation in Czech

    V navrhovaném projektu bude zjišťována organizace transkripčních jednotek a přesná místa počátků transkripce v biosyntetickém shluku linkomycinu. Na základě předchozích výsledků, tzn. znalosti uspořádání genů biosyntézy linkomycinu a částečné znalosti jeho biosyntetické dráhy, byly vytipovány možné regulační geny. Tyto geny budou jednak inaktivovány, jednak bude zvýšována jejich genová dose. Bude sledován vliv těchto zásahů na produkci linkomycinu. K základním metodám navrhovaného projektu patří příprava kosmidové knihovny, inaktivace genů, určení místa počátku transkripce (primer extension), příprava značené cDNA, a hybridizace (microarray). Očekávaným výsledkem projektu je určení regulačních genů linkomycinového biosyntetického shluku a zjištění, jakým způsobem ovlivňují expresi jednotlivých genů shluku a produkci antibiotika. Poznatky o dráhově specifických regulátorech a organizaci transkripčních jednotek umožní cílené manipulace biosyntetické dráhy linkomycinu.

Scientific branches

  • R&D category

    ZV - Basic research

  • CEP classification - main branch

    EB - Genetics and molecular biology

  • CEP - secondary branch

    EE - Microbiology, virology

  • CEP - another secondary branch

    EI - Biotechnology and bionics

  • 10603 - Genetics and heredity (medical genetics to be 3)
    10604 - Reproductive biology (medical aspects to be 3)
    10605 - Developmental biology
    10606 - Microbiology
    10607 - Virology
    10608 - Biochemistry and molecular biology
    10609 - Biochemical research methods
    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
    30101 - Human genetics
    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

    HPLC methods for accurate determination of low quantities of products (lincomycin A and B) and intermediates (4-propyl-L-proline, methylthiolinkosamide, N-demethyl linkomycin and L-DOPA) of the lincomycin biosynthesis were elaborated. The methods were va

Solution timeline

  • Realization period - beginning

    Jan 1, 2005

  • Realization period - end

    Dec 31, 2007

  • Project status

    U - Finished project

  • Latest support payment

    May 2, 2007

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP08-GA0-GA-U/04:3

  • Data delivery date

    Dec 16, 2008

Finance

  • Total approved costs

    2,466 thou. CZK

  • Public financial support

    2,466 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK