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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...

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