tailieunhanh - Báo cáo khoa học: alanine-extradiol cleavage is followed by intramolecular cyclization in lincomycin biosynthesis

The LmbB1 protein, participating in the biosynthesis of lincomycin,was heterologously expressed inEscherichia coli, purified in its active form, and characterized as a dimer of identical subunits. Methods for purification and analysis of the LmbB1 reaction product were developed. Molecular mass and fragmentation pattern of the product revealed by capillary electrophoresis-mass spectrometry were in agree-ment with its proposed structure, 4-(3-carboxy-3-oxo-propenyl)-2,3-dihydro-1H-pyrrole-2-carboxylic acid. The LmbB1 is therefore a dioxygenase catalysing the 2,3-extra-diol cleavage of theL-3,4-dihydroxyphenyl alanine aromatic ring | Eur. J. Biochem. 271 3678-3683 2004 FEBS 2004 doi L-3 4-Dihydroxyphenyl alanine-extradiol cleavage is followed by intramolecular cyclization in lincomycin biosynthesis Jitka Novotna1 Ales Honzatko1 Petr Bednar2 Jan Kopecky1 Jiri Janata1 and Jaroslav Spizek1 Institute of Microbiology Academy of Sciences of the Czech Republic Videnska Praha Czech Republic 2Faculty of Science Palackỷ University Olomouc Czech Republic The LmbB1 protein participating in the biosynthesis of lincomycin was heterologously expressed in Escherichia coli purified in its active form and characterized as a dimer of identical subunits. Methods for purification and analysis of the LmbB1 reaction product were developed. Molecular mass and fragmentation pattern of the product revealed by capillary electrophoresis-mass spectrometry were in agreement with its proposed structure 4- 3-carboxy-3-oxo-propenyl -2 3-dihydro-1H-pyrrole-2-carboxylic acid. The LmbB1 is therefore a dioxygenase catalysing the 2 3-extra-diol cleavage of the L-3 4-dihydroxyphenyl alanine aromatic ring. The final LmbB1 reaction product a unique compound found in biosynthesis of lincomycin and expected in anthramycins arises through subsequent cyclization of the primary cleavage product 2 3-secodopa. A possible role of LmbB1 in 2 3-secodopa cyclization and alternative ways of the cyclization in the formation of biosynthetically related compounds muscaflavin and stizolobinic acid are discussed. Keywords lincomycin L-DOPA derivative of muconic acid semialdehyde 2 3-extradiol dioxygenase 4- 3-carboxy-3-oxo-propenyl -2 3-dihydro-1H-pyrrole-2-carboxylic acid. Lincomycin A and particularly its semisynthetic derivative clindamycin belong to clinically important antibiotics yet our knowledge of lincomycin biosynthesis is rather fragmentary. Structurally lincomycin A is composed of two moieties a sugar moiety 6-amino-6 8-dideoxy-1-thio-D-erythro-a-D-galactooctopyranoside methylthiolincosaminide and an amino

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