KEGG   ORTHOLOGY: K05551Help
Entry
K05551                      KO                                     

Name
actI1, oxyA, tcmK, snoa1, aknB, mtmP
Definition
minimal PKS ketosynthase (KS/KS alpha) [EC:2.3.1.- 2.3.1.260 2.3.1.235]
Pathway
ko00253  Tetracycline biosynthesis
ko01056  Biosynthesis of type II polyketide backbone
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00778  Type II polyketide backbone biosynthesis, acyl-CoA + malonyl-CoA => polyketide
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01056 Biosynthesis of type II polyketide backbone
    K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
   00253 Tetracycline biosynthesis
    K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01004 Lipid biosynthesis proteins
    K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
   01008 Polyketide biosynthesis proteins
    K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
Enzymes [BR:ko01000]
 2. Transferases
  2.3  Acyltransferases
   2.3.1  Transferring groups other than aminoacyl groups
    2.3.1.235  tetracenomycin F2 synthase
     K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
    2.3.1.260  tetracycline polyketide synthase
     K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
    2.3.1.-  
     K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
Lipid biosynthesis proteins [BR:ko01004]
 Polyketide synthase
  Component type
   K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide synthase (PKS)
  Type II PKS
   C7-C12 cyclized polyketide type
    Octaketide PKS
     K05551  actI1, oxyA, tcmK, snoa1, aknB, mtmP; minimal PKS ketosynthase (KS/KS alpha)
BRITE hierarchy
Other DBs
RN: R06635 R06637 R06641 R06643 R06644 R06645 R09258 R09259 R10960 R11516
Genes
MBD: MEBOL_003040
ABF: AMK58_25510
SPAE: E2C16_10950
MSAO: MYCSP_12700
MSAL: DSM43276_02543
NBR: O3I_007445 O3I_015110
NNO: NONO_c10810
NTP: CRH09_08670
NOZ: DMB37_03470
SCO: SCO5087(actIORF1)
SMA: SAVERM_2376(pks9-4)
SFA: Sfla_5318
SBH: SBI_06844
SHY: SHJG_1189
SALS: SLNWT_5121
STRP: F750_1305(whiE-KS)
SALU: DC74_6590
SALL: SAZ_34270
STRE: GZL_p00214
STRD: NI25_18955
SLAU: SLA_3074
SALJ: SMD11_0675(actI1) SMD11_6044(actI1)
LMOI: VV02_05815
TFU: Tfu_1218
TCU: Tcur_2773
SRO: Sros_4150
AMD: AMED_5435(fabF)
AMN: RAM_27705
AMM: AMES_5370(fabF)
AMZ: B737_5370(fabF)
KAL: KALB_7831
ACTI: UA75_11090
ACAD: UA74_11000
ALO: CRK55091
MIL: ML5_4402
ACTN: L083_3109
AG: AAA65206(dpsA) AAF70106(aknB) AAG30189(zhuB) AAZ78325(oxyA) CAA12017(snoa1) CAA61989(mtmP)
 » show all
TaxonomyKoalaUniProt
Reference
PMID:1527048
  Authors
Fernandez-Moreno MA, Martinez E, Boto L, Hopwood DA, Malpartida F
  Title
Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin.
  Journal
J Biol Chem 267:19278-90 (1992)
  Sequence
[sco:SCO5087]
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
Pickens LB, Tang Y
  Title
Oxytetracycline biosynthesis.
  Journal
J Biol Chem 285:27509-15 (2010)
DOI:10.1074/jbc.R110.130419
Reference
PMID:2684656
  Authors
Bibb MJ, Biro S, Motamedi H, Collins JF, Hutchinson CR
  Title
Analysis of the nucleotide sequence of the Streptomyces glaucescens tcmI genes provides key information about the enzymology of polyketide antibiotic biosynthesis.
  Journal
EMBO J 8:2727-36 (1989)
  Sequence
Reference
PMID:8668120
  Authors
Ylihonko K, Tuikkanen J, Jussila S, Cong L, Mantsala P
  Title
A gene cluster involved in nogalamycin biosynthesis from Streptomyces nogalater: sequence analysis and complementation of early-block mutations in the anthracycline pathway.
  Journal
Mol Gen Genet 251:113-20 (1996)
DOI:10.1007/BF02172908
  Sequence
Reference
PMID:8654997
  Authors
Lombo F, Blanco G, Fernandez E, Mendez C, Salas JA
  Title
Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin.
  Journal
Gene 172:87-91 (1996)
DOI:10.1016/0378-1119(96)00029-7
  Sequence

KEGG   ORTHOLOGY: K05552Help
Entry
K05552                      KO                                     

Name
actI2, oxyB, tcmL, snoa2, aknC, mtmK
Definition
minimal PKS chain-length factor (CLF/KS beta) [EC:2.3.1.- 2.3.1.260 2.3.1.235]
Pathway
ko00253  Tetracycline biosynthesis
ko01056  Biosynthesis of type II polyketide backbone
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00778  Type II polyketide backbone biosynthesis, acyl-CoA + malonyl-CoA => polyketide
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01056 Biosynthesis of type II polyketide backbone
    K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
   00253 Tetracycline biosynthesis
    K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01004 Lipid biosynthesis proteins
    K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
   01008 Polyketide biosynthesis proteins
    K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
Enzymes [BR:ko01000]
 2. Transferases
  2.3  Acyltransferases
   2.3.1  Transferring groups other than aminoacyl groups
    2.3.1.235  tetracenomycin F2 synthase
     K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
    2.3.1.260  tetracycline polyketide synthase
     K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
    2.3.1.-  
     K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
Lipid biosynthesis proteins [BR:ko01004]
 Polyketide synthase
  Component type
   K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide synthase (PKS)
  Type II PKS
   C7-C12 cyclized polyketide type
    Octaketide PKS
     K05552  actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta)
BRITE hierarchy
Other DBs
RN: R06635 R06637 R06641 R06643 R06644 R06645 R09258 R09259 R10960 R11516
Genes
MBD: MEBOL_003041
MSAO: MYCSP_12695
MSAL: DSM43276_02542
NBR: O3I_007450 O3I_015115
NNO: NONO_c10800
NTP: CRH09_08675
NOZ: DMB37_03465
SCO: SCO5088(actIORF2)
SMA: SAVERM_2375(pks9-3)
SSX: SACTE_5203 SACTE_6347
SFA: Sfla_5317
SBH: SBI_06845
SHY: SHJG_1188
SVE: SVEN_5981
SALS: SLNWT_5122
STRP: F750_1306(whiE-CLF)
SFI: SFUL_4003
SALU: DC74_6591
SALL: SAZ_34275
STRE: GZL_p00215
STRM: M444_36340
STRD: NI25_18960
SLAU: SLA_3073
SALJ: SMD11_0676(actI2) SMD11_1144(actI2) SMD11_6045(actI2)
LMOI: VV02_05820
TFU: Tfu_1219
TCU: Tcur_2772
SRO: Sros_4151
AMD: AMED_5434(fabF)
AMN: RAM_27700
AMM: AMES_5369(fabF)
AMZ: B737_5369(fabF)
SESP: BN6_54870
KAL: KALB_7830
ACTI: UA75_11095
ACAD: UA74_11005
ALO: CRK55092
MIL: ML5_4403
ACTN: L083_3108
AG: AAA65207(dpsB) AAF70107(aknC) AAG30188(zhuA) AAZ78326(oxyB) CAA12018(snoa2) CAA61990(mtmK)
 » show all
TaxonomyKoalaUniProt
Reference
PMID:1527048
  Authors
Fernandez-Moreno MA, Martinez E, Boto L, Hopwood DA, Malpartida F
  Title
Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin.
  Journal
J Biol Chem 267:19278-90 (1992)
  Sequence
[sco:SCO5088]
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
Pickens LB, Tang Y
  Title
Oxytetracycline biosynthesis.
  Journal
J Biol Chem 285:27509-15 (2010)
DOI:10.1074/jbc.R110.130419
Reference
PMID:2684656
  Authors
Bibb MJ, Biro S, Motamedi H, Collins JF, Hutchinson CR
  Title
Analysis of the nucleotide sequence of the Streptomyces glaucescens tcmI genes provides key information about the enzymology of polyketide antibiotic biosynthesis.
  Journal
EMBO J 8:2727-36 (1989)
  Sequence
Reference
PMID:8668120
  Authors
Ylihonko K, Tuikkanen J, Jussila S, Cong L, Mantsala P
  Title
A gene cluster involved in nogalamycin biosynthesis from Streptomyces nogalater: sequence analysis and complementation of early-block mutations in the anthracycline pathway.
  Journal
Mol Gen Genet 251:113-20 (1996)
DOI:10.1007/BF02172908
  Sequence
Reference
PMID:8654997
  Authors
Lombo F, Blanco G, Fernandez E, Mendez C, Salas JA
  Title
Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin.
  Journal
Gene 172:87-91 (1996)
DOI:10.1016/0378-1119(96)00029-7
  Sequence

KEGG   ORTHOLOGY: K05553Help
Entry
K05553                      KO                                     

Name
actI3, oxyC, tcmM, snoa3, aknD, mtmS
Definition
minimal PKS acyl carrier protein
Pathway
ko00253  Tetracycline biosynthesis
ko01056  Biosynthesis of type II polyketide backbone
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00778  Type II polyketide backbone biosynthesis, acyl-CoA + malonyl-CoA => polyketide
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01056 Biosynthesis of type II polyketide backbone
    K05553  actI3, oxyC, tcmM, snoa3, aknD, mtmS; minimal PKS acyl carrier protein
   00253 Tetracycline biosynthesis
    K05553  actI3, oxyC, tcmM, snoa3, aknD, mtmS; minimal PKS acyl carrier protein
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01004 Lipid biosynthesis proteins
    K05553  actI3, oxyC, tcmM, snoa3, aknD, mtmS; minimal PKS acyl carrier protein
   01008 Polyketide biosynthesis proteins
    K05553  actI3, oxyC, tcmM, snoa3, aknD, mtmS; minimal PKS acyl carrier protein
Lipid biosynthesis proteins [BR:ko01004]
 Polyketide synthase
  Component type
   K05553  actI3, oxyC, tcmM, snoa3, aknD, mtmS; minimal PKS acyl carrier protein
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide synthase (PKS)
  Type II PKS
   C7-C12 cyclized polyketide type
    Octaketide PKS
     K05553  actI3, oxyC, tcmM, snoa3, aknD, mtmS; minimal PKS acyl carrier protein
BRITE hierarchy
Other DBs
RN: R06635 R06637 R06641 R06643 R06644 R06645 R09258 R09259 R10960 R11516
Genes
MBD: MEBOL_003042
MSAO: MYCSP_12690
MSAL: DSM43276_02541
NBR: O3I_007455 O3I_010615 O3I_015120
NNO: NONO_c10790
NTP: CRH09_08680
NOZ: DMB37_03460
SCO: SCO5089(actIORF3)
SMA: SAVERM_2373(pks9-1)
SSX: SACTE_5205 SACTE_6348
SFA: Sfla_5316
SBH: SBI_06846
SHY: SHJG_1187
SVE: SVEN_5982
SALS: SLNWT_5123
STRP: F750_1307
SFI: SFUL_4004
SALU: DC74_6592
SALL: SAZ_34280
SGU: SGLAU_26365(tcmM)
STRE: GZL_p00216
SAMB: SAM23877_0194(alpC) SAM23877_7479(alpC)
STRD: NI25_18965
SLAU: SLA_3072
SALJ: SMD11_0677(actI3) SMD11_1145(actI3) SMD11_6046(actI3)
KSK: KSE_58090
LMOI: VV02_05825
TFU: Tfu_1220
TCU: Tcur_2794
SRO: Sros_4152
AMD: AMED_5433(actI)
AMN: RAM_27695
AMM: AMES_5368(actI)
AMZ: B737_5368(actI)
SESP: BN6_54880(acp5)
KAL: KALB_7829
ACTI: UA75_11100
ACAD: UA74_11010
ALO: CRK55093
MIL: ML5_4404
AG: AAD04718(dpsG) AAF70108(aknD) AAG30201(zhuN) AAZ78327(oxyC) CAA12019(snoa3) CAA61991(mtmS)
 » show all
TaxonomyKoalaUniProt
Reference
PMID:1527048
  Authors
Fernandez-Moreno MA, Martinez E, Boto L, Hopwood DA, Malpartida F
  Title
Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin.
  Journal
J Biol Chem 267:19278-90 (1992)
  Sequence
[sco:SCO5089]
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
Pickens LB, Tang Y
  Title
Oxytetracycline biosynthesis.
  Journal
J Biol Chem 285:27509-15 (2010)
DOI:10.1074/jbc.R110.130419
Reference
PMID:2684656
  Authors
Bibb MJ, Biro S, Motamedi H, Collins JF, Hutchinson CR
  Title
Analysis of the nucleotide sequence of the Streptomyces glaucescens tcmI genes provides key information about the enzymology of polyketide antibiotic biosynthesis.
  Journal
EMBO J 8:2727-36 (1989)
  Sequence
Reference
PMID:1592832
  Authors
Shen B, Summers RG, Gramajo H, Bibb MJ, Hutchinson CR
  Title
Purification and characterization of the acyl carrier protein of the Streptomyces glaucescens tetracenomycin C polyketide synthase.
  Journal
J Bacteriol 174:3818-21 (1992)
DOI:10.1128/JB.174.11.3818-3821.1992
Reference
PMID:8668120
  Authors
Ylihonko K, Tuikkanen J, Jussila S, Cong L, Mantsala P
  Title
A gene cluster involved in nogalamycin biosynthesis from Streptomyces nogalater: sequence analysis and complementation of early-block mutations in the anthracycline pathway.
  Journal
Mol Gen Genet 251:113-20 (1996)
DOI:10.1007/BF02172908
  Sequence
Reference
PMID:8654997
  Authors
Lombo F, Blanco G, Fernandez E, Mendez C, Salas JA
  Title
Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin.
  Journal
Gene 172:87-91 (1996)
DOI:10.1016/0378-1119(96)00029-7
  Sequence

KEGG   ENZYME: 2.3.1.260Help
Entry
EC 2.3.1.260                Enzyme                                 

Name
tetracycline polyketide synthase
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
BRITE hierarchy
Sysname
malonyl-CoA:malonamoyl-[OxyC acyl-carrier protein] malonyltransferase
Reaction(IUBMB)
malonamoyl-[OxyC acyl-carrier protein] + 8 malonyl-CoA = 18-carbamoyl-3,5,7,9,11,13,15,17-octaoxooctadecanoyl-[OxyC acyl-carrier protein] + 8 CO2 + 8 CoA [RN:R11516]
Reaction(KEGG)
Substrate
malonamoyl-[OxyC acyl-carrier protein];
malonyl-CoA [CPD:C00083]
Product
18-carbamoyl-3,5,7,9,11,13,15,17-octaoxooctadecanoyl-[OxyC acyl-carrier protein];
CO2 [CPD:C00011];
CoA [CPD:C00010]
Comment
The synthesis, in the bacterium Streptomyces rimosus, of the tetracycline antibiotics core skeleton requires a minimal polyketide synthase (PKS) consisting of a ketosynthase (KS), a chain length factor (CLF), and an acyl-carrier protein (ACP). Initiation involves an amide-containing starter unit that becomes the C-2 amide that is present in the tetracycline compounds. Following the initiation, the PKS catalyses the iterative condensation of 8 malonyl-CoA molecules to yield the polyketide backbone of tetracycline. Throughout the proccess, the nascent chain is attached to the OxyC acyl-carrier protein.
History
EC 2.3.1.260 created 2016
Pathway
ec00253  Tetracycline biosynthesis
ec01056  Biosynthesis of type II polyketide backbone
ec01100  Metabolic pathways
ec01130  Biosynthesis of antibiotics
Orthology
K05551  minimal PKS ketosynthase (KS/KS alpha)
K05552  minimal PKS chain-length factor (CLF/KS beta)
Genes
MBD: MEBOL_003040 MEBOL_003041
ABF: AMK58_25510
SPAE: E2C16_10950
MSAO: MYCSP_12695 MYCSP_12700
MSAL: DSM43276_02542 DSM43276_02543
NBR: O3I_007445 O3I_007450 O3I_015110 O3I_015115
NNO: NONO_c10800 NONO_c10810
NTP: CRH09_08670 CRH09_08675
NOZ: DMB37_03465 DMB37_03470
SCO: SCO5087(actIORF1) SCO5088(actIORF2)
SMA: SAVERM_2375(pks9-3) SAVERM_2376(pks9-4)
STRP: F750_1305(whiE-KS) F750_1306(whiE-CLF)
STRM: M444_36340
SALJ: SMD11_0675(actI1) SMD11_0676(actI2) SMD11_1144(actI2) SMD11_6044(actI1) SMD11_6045(actI2)
AMD: AMED_5434(fabF) AMED_5435(fabF)
AMM: AMES_5369(fabF) AMES_5370(fabF)
AMZ: B737_5369(fabF) B737_5370(fabF)
 » show all
Taxonomy
Reference
1
  Authors
Thomas, R. and Williams, D.J.
  Title
Oxytetracycline biosynthesis: origin of the carboxamide substituent.
  Journal
J Chem Soc, Chem Commun:677-679 (1983)
Reference
2  [PMID:16597959]
  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
3  [PMID:22500899]
  Authors
Yu L, Cao N, Wang L, Xiao C, Guo M, Chu J, Zhuang Y, Zhang S
  Title
Oxytetracycline biosynthesis improvement in Streptomyces rimosus following duplication of minimal PKS genes.
  Journal
Enzyme Microb Technol 50:318-24 (2012)
DOI:10.1016/j.enzmictec.2012.03.001
Other DBs
ExplorEnz - The Enzyme Database: 2.3.1.260
IUBMB Enzyme Nomenclature: 2.3.1.260
ExPASy - ENZYME nomenclature database: 2.3.1.260
BRENDA, the Enzyme Database: 2.3.1.260

KEGG   REACTION: R11516Help
Entry
R11516                      Reaction                               

Name
malonyl-CoA:malonamoyl-[acyl-carrier protein] malonyltransferase
Definition
Malonamoyl-[acyl-carrier protein] + 8 Malonyl-CoA <=> 18-Carbamoyl-3,5,7,9,11,13,15,17-octaoxooctadecanoyl-[acp] + 8 CO2 + 8 CoA
Equation
C21430 + 8 C00083 <=> C12441 + 8 C00011 + 8 C00010
Comment
There are two proposed pathways for biosynthesis of the malonamate starter unit (see R06641).
Enzyme
Pathway
rn00253  Tetracycline biosynthesis
rn01056  Biosynthesis of type II polyketide backbone
rn01100  Metabolic pathways
rn01130  Biosynthesis of antibiotics
Module
M00778  Type II polyketide backbone biosynthesis, acyl-CoA + malonyl-CoA => polyketide
Orthology
K05551  minimal PKS ketosynthase (KS/KS alpha) [EC:2.3.1.- 2.3.1.260 2.3.1.235]
K05552  minimal PKS chain-length factor (CLF/KS beta) [EC:2.3.1.- 2.3.1.260 2.3.1.235]
K05553  minimal PKS acyl carrier protein
Other DBs
RHEA: 38370

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