Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DECV2ME)

• DME Name: Cytochrome P450 105D7 (cyp105)
• Synonyms: Cytochrome P450 family 105 subfamily D member 7; Pentalenic acid synthase; SAV_7469; cyp105d7; cyp28
• Gene Name: cyp28
• UniProt ID: CYP28_STRAW
• INTEDE ID: DME1233
• EC Number:
  EC: 1.14.15.11
  Oxidoreductase
  Oxygen paired donor oxidoreductase
  Iron-sulfur protein donor oxidoreductase
  EC: 1.14.15.11
• Lineage:
  Species: Streptomyces avermitilis
  Kingdom: Bacteria
  Phylum: Actinobacteria
  Class: Actinobacteria
  Order: Streptomycetales
  Family: Streptomycetaceae
  Genus: Streptomyces
  Species: Streptomyces avermitilis
• Tissue Distribution: Primarily distributed in human gut.
• Sequence:
  MTEPGTSVSAPVAFPQDRTCPYDPPTAYDPLREGRPLSRVSLYDGRSVWVVTGHAAARAL
  LSDQRLSSDRTLPRFPATTERFEAVRTRRVALLGVDDPEHRTQRRMLVPSFTLKRAAALR
  PRIQETVDGLLDAMEAQGPPAELVSAFALPLPSMVICALLGVPYADHDFFESQSRRLLRG
  PGIAEVQDARAQLDDYLYALIDRKRKEPGDGLLDDLIQEQLNRGTVDRAELVSLATLLLI
  AGHETTANMISLGTFTLLRHPEQLAELRAEPGLMPAAVEELLRFLSIADGLLRVATEDIE
  VAGTTIRADEGVVFATSVINRDAAGFAEPDALDWHRSARHHVAFGFGIHQCLGQNLARAE
  MEIALGTLFERLPGLRLAAPADEIPFKPGDTIQGMLELPVTW
• Function: This enzyme is a P-450 heme-thiolate protein, and it catalyzes the conversion of 1-deoxypentalenic acid to pentalenic acid in the biosynthesis of neopentalenolactone antibiotic.
• KEGG Pathway:
  Biosynthesis of secondary metabolites (sma01110)
  Biosynthesis of various secondary metabolites (sma00999)

Molecular Interaction Atlas (MIA) of This DME

1 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[1], [2]

1 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NARINGENIN	DMHAZLM	N. A.	N. A.	Phase 1	[1], [2]

1 Discontinued Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mevastatin	DM1LGKP	N. A.	N. A.	Terminated	[1], [2]

1 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Q-27137207	DML5KMT	N. A.	N. A.	Investigative	[1], [2]

Experimental Enzyme Kinetic Data of Drugs

Drug Name	Indication	Highest Status	Kinetic Data	REF
Mevastatin	N. A.	Terminated	Km = 39.1 microM	[1], [2]
Diclofenac	Chronic renal failure [GB61.Z]	Approved	Kcat/Km = 0.15 s-1microM-1	[1], [2]

References

• [1] The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
• [2] Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis. J Microbiol Biotechnol. 2017 May 28;27(5):956-964.