Information on EC 1.14.13.185 - pikromycin synthase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.14.13.185
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RECOMMENDED NAME
GeneOntology No.
pikromycin synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
10-deoxymethymycin + 2 NADPH + 2 H+ + 2 O2 = novamethymycin + 2 NADP+ + 2 H2O
show the reaction diagram
10-deoxymethymycin + NADPH + H+ + O2 = methymycin + NADP+ + H2O
show the reaction diagram
10-deoxymethymycin + NADPH + H+ + O2 = neomethymycin + NADP+ + H2O
show the reaction diagram
narbomycin + 2 NADPH + 2 H+ + 2 O2 = novapikromyin + 2 NADP+ + 2 H2O
show the reaction diagram
narbomycin + NADPH + H+ + O2 = neopikromycin + NADP+ + H2O
show the reaction diagram
narbomycin + NADPH + H+ + O2 = pikromycin + NADP+ + H2O
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
methymycin, neomethymycin and novamethymycin biosynthesis
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narbomycin, pikromycin and novapikromycin biosynthesis
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Biosynthesis of 12-, 14- and 16-membered macrolides
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
narbomycin,NADH:oxygen oxidoreductase (pikromycin-forming)
A heme-thiolate protein (cytochrome P-450). Involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit. With narbomycin it hydroxylates at either C-12 to give pikromycin or C-14 to give neopikromycin or both positions to give narvopikromycin. With 10-deoxymethymycin it hydroxylates at either C-10 to give methymycin or C-12 to give neomethymycin or both positions to give novamethymycin.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
erythromycin C-12 hydroxylase is able to substitute for pikromycin hydroxylase which is responsible for the hydroxylation of 10-deoxymethymycin and narbomycin. Erythromycin C-12 hydroxylase accepts both 12- and 14-membered macrolides
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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inactivation of pikC gene abolishes production of all hydroxylated macrolides, with corresponding accumulation of 1-deoxymethymycin and narbomycin in the culture medium
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
10-deoxymethymycin + 2 NADPH + 2 H+ + 2 O2
novamethymycin + 2 NADP+ + 2 H2O
show the reaction diagram
10-deoxymethymycin + NADPH + H+ + O2
methymycin + NADP+ + H2O
show the reaction diagram
10-deoxymethymycin + NADPH + H+ + O2
neomethymycin + NADP+ + H2O
show the reaction diagram
narbomycin + 2 NADPH + 2 H+ + 2 O2
novapikromyin + 2 NADP+ + 2 H2O
show the reaction diagram
narbomycin + NADPH + H+ + O2
neopikromycin + NADP+ + H2O
show the reaction diagram
narbomycin + NADPH + H+ + O2
novapikromycin + NADP+ + H2O
show the reaction diagram
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C12,C14-dihydroxylated product of narbomycin
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?
narbomycin + NADPH + H+ + O2
pikromycin + NADP+ + H2O
show the reaction diagram
additional information
?
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erythromycin C-12 hydroxylase is able to substitute for pikromycin hydroxylase which is responsible for the hydroxylation of 10-deoxymethymycin and narbomycin. Erythromycin C-12 hydroxylase accepts both 12- and 14-membered macrolides
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
10-deoxymethymycin + 2 NADPH + 2 H+ + 2 O2
novamethymycin + 2 NADP+ + 2 H2O
show the reaction diagram
O87605
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
10-deoxymethymycin + NADPH + H+ + O2
methymycin + NADP+ + H2O
show the reaction diagram
O87605
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
10-deoxymethymycin + NADPH + H+ + O2
neomethymycin + NADP+ + H2O
show the reaction diagram
O87605
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + 2 NADPH + 2 H+ + 2 O2
novapikromyin + 2 NADP+ + 2 H2O
show the reaction diagram
O87605
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + NADPH + H+ + O2
neopikromycin + NADP+ + H2O
show the reaction diagram
O87605
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + NADPH + H+ + O2
pikromycin + NADP+ + H2O
show the reaction diagram
O87605
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
molecular modeling of the active site. For substrate narbomycin, the hydrophobic residues Ala223, Leu224, Leu225, and Leu226 may form hydrophobic interactions with the methyl group at C-6 and C-8 including C-7 of the macrolide ring
structures of the PikC D50N mutant cocrystallized with narbomycin, to 1.85 A resolution, and with 10-deoxymethymycin, to 3.2 A resolution. In the mutant D50N, the desosamine moiety of both 10-deoxymethymycin and narbomycin is bound in a catalytically productive buried site, suggesting a two-step substrate binding mechanism, whereby desosamine is recognized in the two subsites to allow the macrolide substrate to sequentially progress toward a catalytically favorable orientation
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in a Streptomyces venezuelae pikC mutant
expression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D50N/E85Q
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18.4% conversion of 10-desoxymethymycin, ratio of products neomethymycin to methymycin is 0.38. 3.5% conversion of substrate narbomycin
D50N/E94Q
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no conversion of 10-desoxymethymycin. 5.3% conversion of substrate narbomycin
E85A/E94A
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the mutant enzyme is catalytically incompetent toward both endogenous macrolactone substrates
E94Q
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no conversion of 10-desoxymethymycin. 5.4% conversion of substrate narbomycin