New manumycins by means of the specific genetic screening of natural streptomycete isolates and of the combinatorial biosynthesis
Project goals
The aim of the project is to create a collection of producer strains synthesizing new manumycin-type compounds. About 1/3 - 1/2 of producers will be acquired by means of a genetic screening of streptomycete isolates from various biotopes. The rest shouldbe created based on known or newly discovered producers by methods of gene disruption, mutasynthesis a combinatorial biosynthesis. Next, transfer of entire biosynthetic gene clusters into specialized heterologous producers will be used. Heterologous production quite often affects amounts, structures and ratios of produced metabolites. All producer strains will be subjected to basic genetic characterization, targeted in the genes responsible for the variable components in the structure of manumycins, mainly in the upper polyketide chain, which is the main biological activity determinant. Next, basic parameters of cultivation, fermentation and produced metabolites spectrum will be determined, including structure assessments of their major metabolites.
Keywords
manumycin antibioticspolyketidesstreptomycetesgenetic screeningcombinatorial biosynthesisanti-inflammatory compoundscancerostatics
Public support
Provider
Ministry of Education, Youth and Sports
Programme
KONTAKT II
Call for proposals
KONTAKT II 2 (SMSM2012LH2)
Main participants
Mikrobiologický ústav AV ČR, v. v. i.
Contest type
VS - Public tender
Contract ID
MSMT-6805/2013-311
Alternative language
Project name in Czech
Nové manumyciny cestami specifického genetického screeningu přírodních izolátů streptomycet a kombinatorní biosyntézy
Annotation in Czech
Cílem projektu je vytvoření kolekce producentů nových látek ze skupiny manumycinových antibiotik. Zhruba třetina až polovina produkčních kmenů by měla být získána genetickým screeningem izolátů streptomycet z různých biotopů. Zbytek producentů by měl býtvytvořen na základě známých a nově získaných producentů technikami genové disrupce, mutasyntézy a kombinatoriální biosyntézy. Dalším přístupem je přenos kompletních biosyntetických genových shluků do specializovaných heterologních producentů, při kterémse často mění množství, struktura i vzájemné poměry produkovaných metabolitů. Všechny divoké produkční kmeny by přitom měly projít základní genetickou charakterizací se zaměřením na geny zodpovědné za variabilní oblasti ve struktuře manumycinů, zejménahorní polyketidový řetězec, který je hlavní determinantou biologických aktivit. Dále budou stanoveny základní parametry kultivace, fermentace a spektra produkovaných látek, včetně určení struktury majoritních manumycinových produktů.
Scientific branches
R&D category
ZV - Basic research
CEP classification - main branch
EE - Microbiology, virology
CEP - secondary branch
EB - Genetics and molecular biology
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
V - Vynikající výsledky projektu (s mezinárodním významem atd.)
Project results evaluation
In the project we have screened 1500 natural actinomycete strains and 300 genomes. We have designed methodology of detection and classification of C5N compounds producers. We found and partially analyzed 4 potential manumycins producers, 6 novel producers were designed by combinatorial biosynthesis. Six pure compounds were subjected to anti-inflammatory activity tests. The results were published in 2 impacted articles and as 2 patent applications.
Solution timeline
Realization period - beginning
Mar 1, 2012
Realization period - end
Dec 31, 2015
Project status
U - Finished project
Latest support payment
Feb 27, 2015
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP16-MSM-LH-U/01:1
Data delivery date
Oct 9, 2017
Finance
Total approved costs
2,375 thou. CZK
Public financial support
2,375 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK
Basic information
Recognised costs
2 375 CZK thou.
Public support
2 375 CZK thou.
100%
Provider
Ministry of Education, Youth and Sports
CEP
EE - Microbiology, virology
Solution period
01. 03. 2012 - 31. 12. 2015