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PDBsum entry 4n6e
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Lyase/biosynthetic protein
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PDB id
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4n6e
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References listed in PDB file
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Key reference
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Title
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Co-Opting sulphur-Carrier proteins from primary metabolic pathways for 2-Thiosugar biosynthesis.
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Authors
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E.Sasaki,
X.Zhang,
H.G.Sun,
M.Y.Lu,
T.L.Liu,
A.Ou,
J.Y.Li,
Y.H.Chen,
S.E.Ealick,
H.W.Liu.
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Ref.
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Nature, 2014,
510,
427-431.
[DOI no: ]
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PubMed id
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Abstract
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Sulphur is an essential element for life and is ubiquitous in living systems.
Yet how the sulphur atom is incorporated into many sulphur-containing secondary
metabolites is poorly understood. For bond formation between carbon and sulphur
in primary metabolites, the major ionic sulphur sources are the persulphide and
thiocarboxylate groups on sulphur-carrier (donor) proteins. Each group is
post-translationally generated through the action of a specific activating
enzyme. In all reported bacterial cases, the gene encoding the enzyme that
catalyses the carbon-sulphur bond formation reaction and that encoding the
cognate sulphur-carrier protein exist in the same gene cluster. To study the
production of the 2-thiosugar moiety in BE-7585A, an antibiotic from
Amycolatopsis orientalis, we identified a putative 2-thioglucose synthase, BexX,
whose protein sequence and mode of action seem similar to those of ThiG, the
enzyme that catalyses thiazole formation in thiamine biosynthesis. However, no
gene encoding a sulphur-carrier protein could be located in the BE-7585A
cluster. Subsequent genome sequencing uncovered a few genes encoding
sulphur-carrier proteins that are probably involved in the biosynthesis of
primary metabolites but only one activating enzyme gene in the A. orientalis
genome. Further experiments showed that this activating enzyme can adenylate
each of these sulphur-carrier proteins and probably also catalyses the
subsequent thiolation, through its rhodanese domain. A proper combination of
these sulphur-delivery systems is effective for BexX-catalysed 2-thioglucose
production. The ability of BexX to selectively distinguish sulphur-carrier
proteins is given a structural basis using X-ray crystallography. This study is,
to our knowledge, the first complete characterization of thiosugar formation in
nature and also demonstrates the receptor promiscuity of the A. orientalis
sulphur-delivery system. Our results also show that co-opting the
sulphur-delivery machinery of primary metabolism for the biosynthesis of
sulphur-containing natural products is probably a general strategy found in
nature.
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