KEGG ORTHOLOGY: K16006

ORTHOLOGY: K16006

Entry

K16006            Tight     KO

Symbol

pikC, CYP107L

Name

pikromycin synthase [EC:1.14.15.33]

Pathway

map00522

Biosynthesis of 12-, 14- and 16-membered macrolides

map01052

Type I polyketide structures

map01100

Metabolic pathways

map01110

Biosynthesis of secondary metabolites

Module

M00776

Pikromycin/methymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin

Reaction

R06462

10-deoxymethymycin,reduced ferredoxin:oxygen oxidoreductase (neomethymycin-forming)

R06463

10-deoxymethymycin,reduced ferredoxin:oxygen oxidoreductase (methymycin-forming)

R06464

narbomycin,reduced ferredoxin:oxygen oxidoreductase (pikromycin-forming)

R10626

narbomycin,reduced ferredoxin:oxygen oxidoreductase (neopikromycin-forming)

R10627

narbomycin,reduced ferredoxin:oxygen oxidoreductase (novapikromyin-forming)

R10628

10-deoxymethymycin,reduced ferredoxin:oxygen oxidoreductase (novamethymycin-forming)

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
   01008 Polyketide biosynthesis proteins
    K16006  pikC, CYP107L; pikromycin synthase
   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
Polyketide biosynthesis proteins [BR:ko01008]
Polyketide tailoring proteins
  Oxygenase
   K16006  pikC, CYP107L; pikromycin synthase
Cytochrome P450 [BR:ko00199]
Cytochrome P450, bacteria type
  CYP107 family
   K16006  pikC, CYP107L; pikromycin synthase

Other DBs

COG:

COG2124

Genes

SGX:	H4W23_25485

AG:	AAC68886(pikC)

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

[ag:AAC68886]

Reference

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

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

LinkDB

ENZYME: 1.14.15.33

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

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 = novapikromycin + 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)

R06462 R06463 R06464 R10626 R10627 R10628

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];
novapikromycin [CPD:C20740];
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

ec01110

Biosynthesis of secondary metabolites

Orthology

K16006

pikromycin synthase

Genes

SGX:	H4W23_25485

Reference

1 [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

[ag:AAC68886]

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

LinkDB

REACTION: R06463

Entry

R06463                      Reaction

Name

10-deoxymethymycin,reduced ferredoxin:oxygen oxidoreductase (methymycin-forming)

Definition

10-Deoxymethymycin + 2 Reduced ferredoxin + Oxygen + 2 H+ <=> Methymycin + 2 Oxidized ferredoxin + H2O

Equation

C11994 + 2 C00138 + C00007 + 2 C00080 <=> C11996 + 2 C00139 + C00001

Comment

CYP107L1

Reaction class

RC01526

C11994_C11996

Enzyme

1.14.15.33

Pathway

rn00522

Biosynthesis of 12-, 14- and 16-membered macrolides

rn01100

Metabolic pathways

rn01110

Biosynthesis of secondary metabolites

Module

M00776

Pikromycin/methymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin

Brite

Enzymatic reactions [BR:br08201]
1. Oxidoreductase reactions
  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
     R06463  10-Deoxymethymycin + 2 Reduced ferredoxin + Oxygen + 2 H+ <=> Methymycin + 2 Oxidized ferredoxin + H2O

Orthology

K16006

pikromycin synthase [EC:1.14.15.33]

Other DBs

RHEA:

40542

LinkDB

DBGET integrated database retrieval system