Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026918 (
Mycobacterium
)
52,428
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
myo
-inositol-1-phosphate synthase (MIPS) ortholog
Ari2
, which is encoded in the aristeromycin biosynthetic gene cluster, catalyzes the formation of five-membered cyclitol phosphate using d-fructose 6-phosphate (F6P) as a substrate. To understand the stereochemistry during the
Ari2
reaction
in vivo
, we carried out feeding experiments with (6
S
)-d-[6-
2
H
1
]- and (6
R
)-d-[6-
2
H
1
]glucose in the aristeromycin-producing strain
Streptomyces citricolor
. We observed retention of the
2
H atom of (6
S
)-d-[6-
2
H
1
]glucose and no incorporation of the
2
H atom from (6
R
)-d-[6-
2
H
1
]glucose in aristeromycin. This indicates that
Ari2
abstracts the
pro-R
proton at C6 of F6P after oxidation of C5-OH by nicotinamide adenine dinucleotide (NAD
+
) to generate the enolate intermediate, which then attacks the C2 ketone to form the C-C bond via aldol-type condensation. The reaction of
Ari2
with (6
S
)-d-[6-
2
H
1
]- and (6
R
)-d-[6-
2
H
1
]F6P
in vitro
exhibited identical stereochemistry compared with that observed during the feeding experiments. Furthermore, analysis of the crystal structure of
Ari2
, including NAD
+
as a ligand, revealed the active site of
Ari2
to be similar to that of MIPS of
Mycobacterium
tuberculosis
, supporting the similarity of the reaction mechanisms of
Ari2
and MIPS.
...
PMID:Stereochemistry in the Reaction of the
myo
-Inositol Phosphate Synthase Ortholog Ari2 during Aristeromycin Biosynthesis. 3182 4
