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10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
10-deoxymethymycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novamethymycin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
narbomycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novapikromyin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(4)
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
-
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(5)
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
-
10-deoxymethymycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novamethymycin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
(6)
10-deoxymethymycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novamethymycin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
-
-
-
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(2)
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
-
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1)
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
-
narbomycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novapikromyin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
(3)
narbomycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novapikromyin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
-
-
-
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10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novamethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novapikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
C12,C14-dihydroxylated product of narbomycin
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
narbomycin + reduced ferredoxin [iron-sulfur] cluster + H+ + O2
pikromycin + oxidized ferredoxin [iron-sulfur] cluster + H2O
additional information
?
-
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
with 10-deoxymethymycin it hydroxylates at either C-10 to give methymycin or C-12 to give neomethymycin or both positions to give novamethymycin
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
i.e. YC-17
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
i.e. YC-17. 40% conversion, ratio of products neomethymycin to methymycin is 0.81
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
with 10-deoxymethymycin it hydroxylates at either C-10 to give methymycin or C-12 to give neomethymycin or both positions to give novamethymycin
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
40% conversion, ratio of products neomethymycin to methymycin is 0.81
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novamethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novamethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
with 10-deoxymethymycin it hydroxylates at either C-10 to give methymycin or C-12 to give neomethymycin or both positions to give novamethymycin
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
C14 hydroxylation product of narbomycin
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
with narbomycin the enzyme hydroxylates at either C-12 to give pikromycin or C-14 to give neopikromycin or both positions to give narvopikromycin
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
with narbomycin the enzyme hydroxylates at either C-12 to give pikromycin or C-14 to give neopikromycin or both positions to give narvopikromycin
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
with narbomycin the enzyme hydroxylates at either C-12 to give pikromycin or C-14 to give neopikromycin or both positions to give narvopikromycin
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
binding kinetics are biphasic and accurately described by a double exponential function revealing a fast first phase followed by a slow second one. The kinetic rate of the first binding step, accounting for about 50% of the reaction amplitude, is fast and protein-dependent. The rate of the second step is slow, about 13 per s
35% conversion
-
?
narbomycin + reduced ferredoxin [iron-sulfur] cluster + H+ + O2
pikromycin + oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
narbomycin + reduced ferredoxin [iron-sulfur] cluster + H+ + O2
pikromycin + oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
additional information
?
-
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
-
-
?
additional information
?
-
no catalytic activity with lauric acid. The lauric acid is bound mainly via hydrophobic interactions with the carboxylate group of lauric acid coordinated to the heme of P450. Residue Glu40 and Leu382 in the CYP107L2 complex with lauric acid show significant conformational changes to provide plentiful room for the lauric acid in the substrate-binding site. Binding structure of enzyme, lauric acid and pikromycin, overview
-
-
?
additional information
?
-
-
no catalytic activity with lauric acid. The lauric acid is bound mainly via hydrophobic interactions with the carboxylate group of lauric acid coordinated to the heme of P450. Residue Glu40 and Leu382 in the CYP107L2 complex with lauric acid show significant conformational changes to provide plentiful room for the lauric acid in the substrate-binding site. Binding structure of enzyme, lauric acid and pikromycin, overview
-
-
?
additional information
?
-
no catalytic activity with lauric acid. The lauric acid is bound mainly via hydrophobic interactions with the carboxylate group of lauric acid coordinated to the heme of P450. Residue Glu40 and Leu382 in the CYP107L2 complex with lauric acid show significant conformational changes to provide plentiful room for the lauric acid in the substrate-binding site. Binding structure of enzyme, lauric acid and pikromycin, overview
-
-
?
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10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novamethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit
-
-
?
narbomycin + reduced ferredoxin [iron-sulfur] cluster + H+ + O2
pikromycin + oxidized ferredoxin [iron-sulfur] cluster + H2O
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
-
-
?
narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2
novapikromyin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
-
-
?
narbomycin + reduced ferredoxin [iron-sulfur] cluster + H+ + O2
pikromycin + oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
narbomycin + reduced ferredoxin [iron-sulfur] cluster + H+ + O2
pikromycin + oxidized ferredoxin [iron-sulfur] cluster + H2O
-
-
-
?
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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
purified recombinant ligand-free CYP107L2 and its complex with lauric acid, (1) sitting drop vapor diffusion method, mixing of 500 nl of 12 mg/ml protein solution with 500 nl of reservoir solution containing 0.17 M ammonium sulfate, 0.085 M sodium cacodylate, pH 6.5, 25.5% w/v PEG 8000, and 15% v/v glycerol, for complex crystals lauric acid in a 1:10 M ratio, and equilibration against 0.05 ml of reservoir solution, 14°C, 30 days, (2) hanging drop vapor diffusion method, mixing of 0.001 ml of 12 mg/ml protein solution with 0.001 ml of reservoir solution containing 0.17 M ammonium sulfate, 0.085 M sodium cacodylate, pH 6.5, 25.5% w/v PEG 8000, and 15% v/v glycerol, and equilibration against 0.05 ml of reservoir solution, X-ray diffraction structure determination and analysis at 2.5-2.6 A resolution
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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Lee, S.K.; Basnet, D.B.; Choi, C.Y.; Sohng, J.K.; Ahn, J.S.; Yoon, Y.J.
The role of erythromycin C-12 hydroxylase, EryK, as a substitute for PikC hydroxylase in pikromycin biosynthesis
Bioorg. Chem.
32
549-559
2004
Saccharopolyspora erythraea (P48635)
brenda
Sherman, D.H.; Li, S.; Yermalitskaya, L.V.; Kim, Y.; Smith, J.A.; Waterman, M.R.; Podust, L.M.
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae
J. Biol. Chem.
281
26289-26297
2006
Streptomyces venezuelae (O87605)
brenda
Xue, Y.; Wilson, D.; Zhao, L.; Liu, H.w.; Sherman, D.H.
Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae
Chem. Biol.
5
661-667
1998
Streptomyces venezuelae (O87605)
brenda
Li, S.; Ouellet, H.; Sherman, D.H.; Podust, L.M.
Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae
J. Biol. Chem.
284
5723-5730
2009
Streptomyces venezuelae (O87605)
brenda
Lee, S.K.; Park, J.W.; Kim, J.W.; Jung, W.S.; Park, S.R.; Choi, C.Y.; Kim, E.S.; Kim, B.S.; Ahn, J.S.; Sherman, D.H.; Yoon, Y.J.
Neopikromycin and novapikromycin from the pikromycin biosynthetic pathway of Streptomyces venezuelae
J. Nat. Prod.
69
847-849
2006
Streptomyces venezuelae (O87605)
brenda
Han, S.; Pham, T.V.; Kim, J.H.; Lim, Y.R.; Park, H.G.; Jeong, D.; Yun, C.H.; Chun, Y.J.; Kang, L.W.; Kim, D.
Structural insights into the binding of lauric acid to CYP107L2 from Streptomyces avermitilis
Biochem. Biophys. Res. Commun.
482
902-908
2017
Streptomyces avermitilis (Q82LM3), Streptomyces avermitilis, Streptomyces avermitilis ATCC 31267 (Q82LM3)
brenda
1.14.15.33 pikromycin synthase
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