KEGG   ORTHOLOGY: K15981Help
Entry
K15981                      KO                                     

Name
CYP125A
Definition
cholest-4-en-3-one 26-monooxygenase [EC:1.14.15.29]
Pathway
ko00984  Steroid degradation
ko01120  Microbial metabolism in diverse environments
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09111 Xenobiotics biodegradation and metabolism
   00984 Steroid degradation
    K15981  CYP125A; cholest-4-en-3-one 26-monooxygenase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   00199 Cytochrome P450
    K15981  CYP125A; cholest-4-en-3-one 26-monooxygenase
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
    1.14.15.29  cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]
     K15981  CYP125A; cholest-4-en-3-one 26-monooxygenase
Cytochrome P450 [BR:ko00199]
 Cytochrome P450, bacteria type
  CYP125 family
   K15981  CYP125A; cholest-4-en-3-one 26-monooxygenase
BRITE hierarchy
Other DBs
RN: R11357
COG: COG2124
Genes
ZAL: AZF00_12765
HJA: BST95_05650 BST95_12090
MTU: Rv3545c(cyp125)
MTV: RVBD_3545c
MTC: MT3649
MRA: MRA_3584(cyp125)
MTF: TBFG_13578
MTB: TBMG_03584
MTK: TBSG_03611
MTZ: TBXG_003560
MTUR: CFBS_3761(cyp125)
MTO: MTCTRI2_3609(cyp125)
MTD: UDA_3545c(cyp125)
MTN: ERDMAN_3890(cyp125)
MTUC: J113_24790
MTUE: J114_18960
MTUH: I917_24870
MTUL: TBHG_03485
MTUT: HKBT1_3746(cyp125)
MTUU: HKBT2_3755(cyp125)
MTQ: HKBS1_3758(cyp125)
MBO: BQ2027_MB3575C(cyp125)
MBB: BCG_3609c(cyp125)
MBT: JTY_3610(cyp125)
MBM: BCGMEX_3607c(cyp125)
MBX: BCGT_3411
MAF: MAF_35570(cyp125)
MMIC: RN08_3921
MCE: MCAN_35561(cyp125)
MCQ: BN44_110037(cyp)
MCV: BN43_90043(cyp)
MCX: BN42_90040(cyp)
MCZ: BN45_100040(cyp)
MLP: MLM_0760
MUL: MUL_4106(cyp125A7)
MMI: MMAR_2783(cyp125A6) MMAR_5032(cyp125A7)
MMAE: MMARE11_27030(cyp125A6) MMARE11_48420(cyp125A7)
MLI: MULP_02541(cyp125A6) MULP_05284(cyp125A7)
MSG: MSMEI_3443(cyp125) MSMEI_5695(cyp125) MSMEI_5834(cyp125)
MJD: JDM601_2803(cyp125A7) JDM601_3609(cyp125A7) JDM601_3682(cyp125A7) JDM601_3692(cyp125A7) JDM601_3693(cyp125A7)
MTER: 4434518_02769(cyp125A7_1) 4434518_03588(cyp125A7_2) 4434518_03654(cyp125A7_3) 4434518_03664(cyp125A7_4) 4434518_03665(cyp125A7_5)
ASD: AS9A_0965
ROP: ROP_47780
GBR: Gbro_3970
GOR: KTR9_3902(cyp125A1)
TPR: Tpau_3821
SMA: SAVERM_5841(cyp22)
SGR: SGR_5169
SGB: WQO_09525
SCT: SCAT_1444(cyp)
SBH: SBI_07560(cyp37)
SHY: SHJG_3828
SVE: SVEN_2047
SDV: BN159_6030(cyp125)
SFI: SFUL_1917
SALU: DC74_2810
SALL: SAZ_15430
STRE: GZL_06167
SLD: T261_5756
STRM: M444_11810
SPRI: SPRI_5168
SNR: SNOUR_28615(cyp125)
SMAL: SMALA_2275
SLAU: SLA_1953
SALJ: SMD11_4755
SFK: KY5_2401
NCA: Noca_2739
PSIM: KR76_14335
TCU: Tcur_3656
SRO: Sros_8218
AMD: AMED_2551
AMN: RAM_12965
AMM: AMES_2524
AMZ: B737_2525
AOI: AORI_2528
AJA: AJAP_26185(cyp125)
KAL: KALB_3393
ALO: CRK59579
SAQ: Sare_2811
CAI: Caci_0773
AG: ACU30137(CYP125)
 » show all
TaxonomyKoalaUniProt
Reference
  Authors
Capyk JK, Kalscheuer R, Stewart GR, Liu J, Kwon H, Zhao R, Okamoto S, Jacobs WR Jr, Eltis LD, Mohn WW
  Title
Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids.
  Journal
J Biol Chem 284:35534-42 (2009)
DOI:10.1074/jbc.M109.072132
  Sequence
[mtu:Rv3545c]
Reference
  Authors
Rosloniec KZ, Wilbrink MH, Capyk JK, Mohn WW, Ostendorf M, van der Geize R, Dijkhuizen L, Eltis LD
  Title
Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHA1.
  Journal
Mol Microbiol 74:1031-43 (2009)
DOI:10.1111/j.1365-2958.2009.06915.x
  Sequence

KEGG   ENZYME: 1.14.15.29Help
Entry
EC 1.14.15.29               Enzyme                                 

Name
cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming];
CYP125;
CYP125A1;
cholest-4-en-3-one 27-monooxygenase (misleading);
cholest-4-en-3-one,NADH:oxygen oxidoreductase (26-hydroxylating);
cholest-4-en-3-one 26-monooxygenase (ambiguous)
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
cholest-4-en-3-one,[reduced ferredoxin]:oxygen oxidoreductase [(25S)-3-oxocholest-4-en-26-oate forming]
Reaction(IUBMB)
cholest-4-en-3-one + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2 = (25S)-3-oxocholest-4-en-26-oate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O (overall reaction) [RN:R11357];
(1a) cholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-hydroxycholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O [RN:R09859];
(1b) (25S)-26-hydroxycholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-oxocholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O [RN:R11355];
(1c) (25S)-26-oxocholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-3-oxocholest-4-en-26-oate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O [RN:R11356]
Reaction(KEGG)
Substrate
cholest-4-en-3-one [CPD:C00599];
reduced ferredoxin [iron-sulfur] cluster [CPD:C00138];
H+ [CPD:C00080];
O2 [CPD:C00007];
(25S)-26-hydroxycholest-4-en-3-one [CPD:C20143];
(25S)-26-oxocholest-4-en-3-one [CPD:C21304]
Product
(25S)-3-oxocholest-4-en-26-oate [CPD:C21076];
oxidized ferredoxin [iron-sulfur] cluster [CPD:C00139];
H2O [CPD:C00001];
(25S)-26-hydroxycholest-4-en-3-one [CPD:C20143];
(25S)-26-oxocholest-4-en-3-one [CPD:C21304]
Comment
A cytochrome P-450 (heme-thiolate) protein found in several bacterial pathogens. The enzyme is involved in degradation of the host's cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol [4]. The products are exclusively in the (25S) configuration. The enzyme is part of a two-component system that also includes a ferredoxin reductase (most likely KshB, which also interacts with EC 1.14.15.30, 3-ketosteroid 9alpha-monooxygenase). The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.15.28, cholest-4-en-3-one 27-monooxygenase.
History
EC 1.14.15.29 created 2012 as EC 1.14.13.141, modified 2016, transferred 2018 to EC 1.14.15.29
Pathway
ec00984  Steroid degradation
ec01120  Microbial metabolism in diverse environments
Orthology
K15981  cholest-4-en-3-one 26-monooxygenase
Genes
ZAL: AZF00_12765
HJA: BST95_05650 BST95_12090
MTU: Rv3545c(cyp125)
MTV: RVBD_3545c
MTC: MT3649
MRA: MRA_3584(cyp125)
MTF: TBFG_13578
MTB: TBMG_03584
MTK: TBSG_03611
MTZ: TBXG_003560
MTUR: CFBS_3761(cyp125)
MTO: MTCTRI2_3609(cyp125)
MTD: UDA_3545c(cyp125)
MTN: ERDMAN_3890(cyp125)
MTUC: J113_24790
MTUE: J114_18960
MTUH: I917_24870
MTUL: TBHG_03485
MTUT: HKBT1_3746(cyp125)
MTUU: HKBT2_3755(cyp125)
MTQ: HKBS1_3758(cyp125)
MBO: BQ2027_MB3575C(cyp125)
MBB: BCG_3609c(cyp125)
MBT: JTY_3610(cyp125)
MBM: BCGMEX_3607c(cyp125)
MBX: BCGT_3411
MAF: MAF_35570(cyp125)
MMIC: RN08_3921
MCE: MCAN_35561(cyp125)
MCQ: BN44_110037(cyp)
MCV: BN43_90043(cyp)
MCX: BN42_90040(cyp)
MCZ: BN45_100040(cyp)
MLP: MLM_0760
MUL: MUL_4106(cyp125A7)
MMI: MMAR_2783(cyp125A6) MMAR_5032(cyp125A7)
MMAE: MMARE11_27030(cyp125A6) MMARE11_48420(cyp125A7)
MLI: MULP_02541(cyp125A6) MULP_05284(cyp125A7)
MSG: MSMEI_3443(cyp125) MSMEI_5695(cyp125) MSMEI_5834(cyp125)
MJD: JDM601_2803(cyp125A7) JDM601_3609(cyp125A7) JDM601_3682(cyp125A7) JDM601_3692(cyp125A7) JDM601_3693(cyp125A7)
MTER: 4434518_02769(cyp125A7_1) 4434518_03588(cyp125A7_2) 4434518_03654(cyp125A7_3) 4434518_03664(cyp125A7_4) 4434518_03665(cyp125A7_5)
ASD: AS9A_0965
ROP: ROP_47780
GBR: Gbro_3970
GOR: KTR9_3902(cyp125A1)
TPR: Tpau_3821
SMA: SAVERM_5841(cyp22)
SGR: SGR_5169
SGB: WQO_09525
SCT: SCAT_1444(cyp)
SBH: SBI_07560(cyp37)
SHY: SHJG_3828
SVE: SVEN_2047
SDV: BN159_6030(cyp125)
SFI: SFUL_1917
SALU: DC74_2810
SALL: SAZ_15430
STRE: GZL_06167
SLD: T261_5756
STRM: M444_11810
SPRI: SPRI_5168
SNR: SNOUR_28615(cyp125)
SMAL: SMALA_2275
SLAU: SLA_1953
SALJ: SMD11_4755
SFK: KY5_2401
NCA: Noca_2739
PSIM: KR76_14335
TCU: Tcur_3656
SRO: Sros_8218
AMD: AMED_2551
AMN: RAM_12965
AMM: AMES_2524
AMZ: B737_2525
AOI: AORI_2528
AJA: AJAP_26185(cyp125)
KAL: KALB_3393
ALO: CRK59579
SAQ: Sare_2811
CAI: Caci_0773
 » show all
Taxonomy
Reference
1  [PMID:19843222]
  Authors
Rosloniec KZ, Wilbrink MH, Capyk JK, Mohn WW, Ostendorf M, van der Geize R, Dijkhuizen L, Eltis LD
  Title
Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHA1.
  Journal
Mol Microbiol 74:1031-43 (2009)
DOI:10.1111/j.1365-2958.2009.06915.x
  Sequence
Reference
2  [PMID:19846552]
  Authors
McLean KJ, Lafite P, Levy C, Cheesman MR, Mast N, Pikuleva IA, Leys D, Munro AW
  Title
The Structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection.
  Journal
J Biol Chem 284:35524-33 (2009)
DOI:10.1074/jbc.M109.032706
  Sequence
[mtu:Rv3545c]
Reference
3  [PMID:19846551]
  Authors
Capyk JK, Kalscheuer R, Stewart GR, Liu J, Kwon H, Zhao R, Okamoto S, Jacobs WR Jr, Eltis LD, Mohn WW
  Title
Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids.
  Journal
J Biol Chem 284:35534-42 (2009)
DOI:10.1074/jbc.M109.072132
  Sequence
[mtu:Rv3545c]
Reference
4  [PMID:20545858]
  Authors
Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust LM, de Montellano PR
  Title
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies  intracellularly generated cholest-4-en-3-one.
  Journal
Mol Microbiol 77:730-42 (2010)
DOI:10.1111/j.1365-2958.2010.07243.x
  Sequence
[mtu:Rv3545c]
Other DBs
ExplorEnz - The Enzyme Database: 1.14.15.29
IUBMB Enzyme Nomenclature: 1.14.15.29
ExPASy - ENZYME nomenclature database: 1.14.15.29
BRENDA, the Enzyme Database: 1.14.15.29

KEGG   REACTION: R11357Help
Entry
R11357                      Reaction                               

Name
cholest-4-en-3-one,[reduced ferredoxin]:oxygen oxidoreductase [(25S)-3-oxocholest-4-en-26-oate forming]
Definition
Cholest-4-en-3-one + 6 Reduced ferredoxin + 6 H+ + 3 Oxygen <=> Delta4-Dafachronic acid + 6 Oxidized ferredoxin + 4 H2O
Equation
C00599 + 6 C00138 + 6 C00080 + 3 C00007 <=> C21076 + 6 C00139 + 4 C00001
Comment
three-step reaction (see R09859+R11355+R11356)
Reaction class
RC03368  C00599_C21076
Enzyme
Pathway
rn00984  Steroid degradation
rn01120  Microbial metabolism in diverse environments
Orthology
K15981  cholest-4-en-3-one 26-monooxygenase [EC:1.14.15.29]
Other DBs
RHEA: 51567

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