KEGG   ORTHOLOGY: K16006Help
Entry
K16006                      KO                                     

Name
pikC, CYP107L
Definition
pikromycin synthase [EC:1.14.15.33]
Pathway
ko00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ko01052  Type I polyketide structures
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00776  Pikromycin/methymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01052 Type I polyketide structures
    K16006  pikC, CYP107L; pikromycin synthase
   00522 Biosynthesis of 12-, 14- and 16-membered macrolides
    K16006  pikC, CYP107L; pikromycin synthase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   00199 Cytochrome P450
    K16006  pikC, CYP107L; pikromycin synthase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.15  With reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen into the other donor
    1.14.15.33  pikromycin synthase
     K16006  pikC, CYP107L; pikromycin synthase
Cytochrome P450 [BR:ko00199]
 Cytochrome P450, bacteria type
  CYP107 family
   K16006  pikC, CYP107L; pikromycin synthase
BRITE hierarchy
Other DBs
RN: R06462 R06463 R06464 R10626 R10627 R10628
COG: COG2124
Genes
AG: AAC68886(pikC)
TaxonomyKoalaUniProt
Reference
PMID:9831532
  Authors
Xue Y, Wilson D, Zhao L, Liu H, Sherman DH
  Title
Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae.
  Journal
Chem Biol 5:661-7 (1998)
DOI:10.1016/S1074-5521(98)90293-9
  Sequence
Reference
  Authors
Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust LM
  Title
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae.
  Journal
J Biol Chem 281:26289-97 (2006)
DOI:10.1074/jbc.M605478200
Reference
  Authors
Li S, Ouellet H, Sherman DH, Podust LM
  Title
Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae.
  Journal
J Biol Chem 284:5723-30 (2009)
DOI:10.1074/jbc.M807592200

KEGG   ENZYME: 1.14.15.33Help
Entry
EC 1.14.15.33               Enzyme                                 

Name
pikromycin synthase;
PikC;
CYP107L1
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
narbomycin,reduced ferredoxin:oxygen oxidoreductase (pikromycin-forming)
Reaction(IUBMB)
(1) narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O [RN:R06464];
(2) narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O [RN:R10626];
(3) narbomycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novapikromyin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O [RN:R10627];
(4) 10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O [RN:R06463];
(5) 10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O [RN:R06462];
(6) 10-deoxymethymycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novamethymycin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O [RN:R10628]
Reaction(KEGG)
Substrate
narbomycin [CPD:C11998];
reduced ferredoxin [iron-sulfur] cluster [CPD:C00138];
H+ [CPD:C00080];
O2 [CPD:C00007];
10-deoxymethymycin [CPD:C11994]
Product
pikromycin [CPD:C11999];
oxidized ferredoxin [iron-sulfur] cluster [CPD:C00139];
H2O [CPD:C00001];
neopikromycin [CPD:C20739];
novapikromyin;
methymycin [CPD:C11996];
neomethymycin [CPD:C11995];
novamethymycin [CPD:C20741]
Comment
A cytochrome P-450 (heme-thiolate) protein. 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.
History
EC 1.14.15.33 created 2014 as EC 1.14.13.185, transferred 2018 to EC 1.14.15.33
Pathway
ec00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ec01100  Metabolic pathways
ec01130  Biosynthesis of antibiotics
Orthology
K16006  pikromycin synthase
Reference
1  [PMID:9831532]
  Authors
Xue Y, Wilson D, Zhao L, Liu Hw, Sherman DH
  Title
Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae.
  Journal
Chem Biol 5:661-7 (1998)
DOI:10.1016/S1074-5521(98)90293-9
  Sequence
Reference
2  [PMID:16825192]
  Authors
Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust LM
  Title
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae.
  Journal
J Biol Chem 281:26289-97 (2006)
DOI:10.1074/jbc.M605478200
Reference
3  [PMID:19124459]
  Authors
Li S, Ouellet H, Sherman DH, Podust LM
  Title
Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae.
  Journal
J Biol Chem 284:5723-30 (2009)
DOI:10.1074/jbc.M807592200
Other DBs
ExplorEnz - The Enzyme Database: 1.14.15.33
IUBMB Enzyme Nomenclature: 1.14.15.33
ExPASy - ENZYME nomenclature database: 1.14.15.33
BRENDA, the Enzyme Database: 1.14.15.33

KEGG   REACTION: R06464Help
Entry
R06464                      Reaction                               

Name
narbomycin,reduced ferredoxin:oxygen oxidoreductase (pikromycin-forming)
Definition
Narbomycin + 2 Reduced ferredoxin + 2 H+ + Oxygen <=> Pikromycin + 2 Oxidized ferredoxin + H2O
Equation
Comment
CYP107L1
Reaction class
RC01526  C11998_C11999
Enzyme
Pathway
rn00522  Biosynthesis of 12-, 14- and 16-membered macrolides
rn01100  Metabolic pathways
rn01130  Biosynthesis of antibiotics
Module
M00776  Pikromycin/methymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin
Orthology
K16006  pikromycin synthase [EC:1.14.15.33]
Other DBs
RHEA: 39890

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