KEGG   ORTHOLOGY: K14256
Entry
K14256                      KO                                     
Symbol
oxyS, cts8
Name
anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase [EC:1.14.13.38 1.14.13.234]
Pathway
map00253  Tetracycline biosynthesis
map01057  Biosynthesis of type II polyketide products
map01100  Metabolic pathways
map01110  Biosynthesis of secondary metabolites
Module
M00780  Tetracycline/oxytetracycline biosynthesis, pretetramide => tetracycline/oxytetracycline
M00823  Chlortetracycline biosynthesis, pretetramide => chlortetracycline
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01057 Biosynthesis of type II polyketide products
    K14256  oxyS, cts8; anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase
   00253 Tetracycline biosynthesis
    K14256  oxyS, cts8; anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01008 Polyketide biosynthesis proteins
    K14256  oxyS, cts8; anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.13  With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
    1.14.13.38  anhydrotetracycline 6-monooxygenase
     K14256  oxyS, cts8; anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase
    1.14.13.234  5a,11a-dehydrotetracycline 5-monooxygenase
     K14256  oxyS, cts8; anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide tailoring proteins
  Oxygenase
   K14256  oxyS, cts8; anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase
Other DBs
RN: R04060 R09198
GO: 0047670
Genes
SVR: CP971_23960
SRIM: CP984_02460
SPLA: CP981_34445
SACT: DMT42_19730
KAU: B6264_18535
NEX: NE857_24350
AGRA: AGRA3207_005105 AGRA3207_005106
AORI: SD37_34210
CCAZ: COUCH_15960
AG: AAZ78342(oxyS) AEI98657(ctcN) BAA07387(cts8)
Reference
  Authors
Zhang W, Ames BD, Tsai SC, Tang Y
  Title
Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase.
  Journal
Appl Environ Microbiol 72:2573-80 (2006)
DOI:10.1128/AEM.72.4.2573-2580.2006
  Sequence
Reference
  Authors
Peric-Concha N, Borovicka B, Long PF, Hranueli D, Waterman PG, Hunter IS
  Title
Ablation of the otcC gene encoding a post-polyketide hydroxylase from the oxytetracyline biosynthetic pathway in Streptomyces rimosus results in novel polyketides with altered chain length.
  Journal
J Biol Chem 280:37455-60 (2005)
DOI:10.1074/jbc.M503191200
Reference
  Authors
Wang P, Bashiri G, Gao X, Sawaya MR, Tang Y
  Title
Uncovering the enzymes that catalyze the final steps in oxytetracycline biosynthesis.
  Journal
J Am Chem Soc 135:7138-41 (2013)
DOI:10.1021/ja403516u

KEGG   ENZYME: 1.14.13.234
Entry
EC 1.14.13.234              Enzyme                                 
Name
5a,11a-dehydrotetracycline 5-monooxygenase;
oxyS (gene name);
12-dehydrotetracycline 5-monooxygenase
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
Sysname
5a,11a-dehydrotetracycline,NADPH:oxygen oxidoreductase (5-hydroxylating)
Reaction(IUBMB)
5a,11a-dehydrotetracycline + NADPH + H+ + O2 = 5a,11a-dehydrooxytetracycline + NADP+ + H2O [RN:R09198]
Reaction(KEGG)
R09198
Substrate
5a,11a-dehydrotetracycline [CPD:C03206];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007]
Product
5a,11a-dehydrooxytetracycline [CPD:C18296];
NADP+ [CPD:C00006];
H2O [CPD:C00001]
Comment
The enzyme, characterized from the bacterium Streptomyces rimosus, is bifunctional, catalysing two successive monooxygenation reactions. It starts by catalysing the stereospecific hydroxylation of anhydrotetracycline at C-6 (EC 1.14.13.38). If the released product is captured by EC 1.3.98.4, 5a,11a-dehydrotetracycline dehydrogenase (OxyR), it is reduced to tetracycline. However, if the released product is recaptured by OxyS, it performs an additional hydroxylation at C-5, producing 5a,11a-dehydrooxytetracycline, which, following the action of OxyR, becomes oxytetracycline.
History
EC 1.14.13.234 created 2016
Pathway
ec00253  Tetracycline biosynthesis
ec01057  Biosynthesis of type II polyketide products
ec01100  Metabolic pathways
ec01110  Biosynthesis of secondary metabolites
Orthology
K14256  anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase
Genes
SVRCP971_23960
SRIMCP984_02460
SPLACP981_34445
SACTDMT42_19730
KAUB6264_18535
NEXNE857_24350
AGRAAGRA3207_005105 AGRA3207_005106
AORISD37_34210
CCAZCOUCH_15960
Reference
1  [PMID:2914874]
  Authors
Binnie C, Warren M, Butler MJ
  Title
Cloning and heterologous expression in Streptomyces lividans of Streptomyces rimosus genes involved in oxytetracycline biosynthesis.
  Journal
J Bacteriol 171:887-95 (1989)
DOI:10.1128/JB.171.2.887-895.1989
Reference
2  [PMID:4959040]
  Authors
Miller PA, Saturnelli A, Martin JH, Itscher LA, Bohonos N
  Title
A new family of tetracycline precursors. N-demethylanhydrotetracyclines.
  Journal
Biochem Biophys Res Commun 16:285-91 (1964)
DOI:10.1016/0006-291X(64)90341-9
Reference
3  [PMID:3138982]
  Authors
Vancurova I, Volc J, Flieger M, Neuzil J, Novotna J, Vlach J, Behal V
  Title
Isolation of pure anhydrotetracycline oxygenase from Streptomyces aureofaciens.
  Journal
Biochem J 253:263-7 (1988)
DOI:10.1042/bj2530263
Reference
4  [PMID:23621493]
  Authors
Wang P, Bashiri G, Gao X, Sawaya MR, Tang Y
  Title
Uncovering the enzymes that catalyze the final steps in oxytetracycline biosynthesis.
  Journal
J Am Chem Soc 135:7138-41 (2013)
DOI:10.1021/ja403516u
Other DBs
ExplorEnz - The Enzyme Database: 1.14.13.234
IUBMB Enzyme Nomenclature: 1.14.13.234
ExPASy - ENZYME nomenclature database: 1.14.13.234
BRENDA, the Enzyme Database: 1.14.13.234

KEGG   REACTION: R09198
Entry
R09198                      Reaction                               
Name
5a,11a-dehydrotetracycline,NADPH:oxygen oxidoreductase (5-hydroxylating)
Definition
5a,11a-Dehydrotetracycline + NADPH + H+ + Oxygen <=> 5a,11a-Dehydrooxytetracycline + NADP+ + H2O
Equation
Reaction class
RC02085  C03206_C18296
Enzyme
Pathway
rn00253  Tetracycline biosynthesis
rn01057  Biosynthesis of type II polyketide products
rn01100  Metabolic pathways
rn01110  Biosynthesis of secondary metabolites
Module
M00780  Tetracycline/oxytetracycline biosynthesis, pretetramide => tetracycline/oxytetracycline
Orthology
K14256  anhydrotetracycline 6-monooxygenase / 5a,11a-dehydrotetracycline 5-monooxygenase [EC:1.14.13.38 1.14.13.234]

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