|
|
Mutational analysis of manumycin antibiotics biosynthetic routes
Kolek, Jan ; Petříček, Miroslav (advisor) ; Zikánová, Blanka (referee)
Mutational analysis of manumycin antibiotics biosynthetic routes The manumycin antibiotics are secondary metabolites, which come from a big group of polyketide metabolites. They are produced by bacteria from genus Streptomyces. Manumycin antibiotics are characterized by two linear polyketide chains, which are connected to a central mC7N moiety. The lower chain is often terminated by the C5N moiety. Manumycin metabolites show many biological activities. They have antimicrobial activity, especially against gram-positive bacteria. Next, they posses antifungal, insecticidal or antiinflamatory activities. Manumycins are also potentional anticancer agents. In order to prepare these compounds by the fermentation, the detailed knowledge of their biosynthetic routes is required. Mutational analysis is based on techniques of genetic engineering. Mutational analysis is a useful pool for analysis of biosynthetic pathways of secondary metabolites and the genes, which are involved in these pathways. This knowledge is essential for application of combinatorial biosynthesis for the design of new metabolites. The new hybrid compound could be used in future as new antibiotics or anticancer drugs. Keywords: manumycin, polyketide, streptomyces, asukamycin
|
|
|
Biosynthesis of lower polyketide chains in manumycin antibiotics - the length-affecting factors
Kolek, Jan ; Petříček, Miroslav (advisor) ; Seydlová, Gabriela (referee)
Manumycin antibiotics represent an important class of secondary metabolites produced by Streptomyces bacteria. They belong to a big class of polyketide metabolites and posses significant antimicrobial, anti-inflammatory, antitumor, and many other biological activities. They are characterized by two short polyketide chains, which are attached to a central subunit. Polyketide chains are synthesized by enzymes of the iterative type II polyketide-synthase. Mechanism of regulation of the polyketide chains length has not been known yet. Understanding mechanism can lead to biosynthesis of novel manumycin antibiotics with predetermined chain lengths what may improve their biological activities in favour of a practical use of these compounds. We prepared a mutant strain of asukamycin producer Streptomyces nodosus ssp. asukaensis with deletion of genes coding for type I/II β-ketoacylsynthase and protein AsuC14, which is a potential factor affecting lower polyketide chain length, for the identification of the chain length factor in manumycin antibiotics producers. Next, the genes for type I/II β-ketoacylsynthase and potential chain length-affecting factor C14 from strains producing manumycins with variable length of the lower polyketide chains were expressed in this mutant strain. Our results demonstrate...
|
|
|
Mutational analysis of manumycin antibiotics biosynthetic routes
Kolek, Jan ; Petříček, Miroslav (advisor) ; Zikánová, Blanka (referee)
Mutational analysis of manumycin antibiotics biosynthetic routes The manumycin antibiotics are secondary metabolites, which come from a big group of polyketide metabolites. They are produced by bacteria from genus Streptomyces. Manumycin antibiotics are characterized by two linear polyketide chains, which are connected to a central mC7N moiety. The lower chain is often terminated by the C5N moiety. Manumycin metabolites show many biological activities. They have antimicrobial activity, especially against gram-positive bacteria. Next, they posses antifungal, insecticidal or antiinflamatory activities. Manumycins are also potentional anticancer agents. In order to prepare these compounds by the fermentation, the detailed knowledge of their biosynthetic routes is required. Mutational analysis is based on techniques of genetic engineering. Mutational analysis is a useful pool for analysis of biosynthetic pathways of secondary metabolites and the genes, which are involved in these pathways. This knowledge is essential for application of combinatorial biosynthesis for the design of new metabolites. The new hybrid compound could be used in future as new antibiotics or anticancer drugs. Keywords: manumycin, polyketide, streptomyces, asukamycin
|
guest ::
