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The biosynthesis of acarbose and validamycin
Author(s) -
Mahmud Taifo,
Lee Sungsook,
Floss Heinz G.
Publication year - 2001
Publication title -
the chemical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.61
H-Index - 78
eISSN - 1528-0691
pISSN - 1527-8999
DOI - 10.1002/tcr.1015
Subject(s) - acarbose , aminocyclitol , moiety , chemistry , stereochemistry , biosynthesis , biochemistry , enzyme , aminoglycoside , antibiotics
The studies reported here have established the biosynthetic origin of the mC 7 N units of acarbose and validamycin from sedo‐ heptulose 7‐phosphate, and have identified 2‐ epi ‐5‐ epi ‐valiolone as the initial cyclization product. The deoxyhexose moiety of acarbose arises from glucose with deoxythymidyl‐diphospho‐4‐keto‐6‐deoxy‐D‐glucose (dTDP‐4‐keto‐6‐deoxy‐D‐glucose) as a proximate intermediate. However, despite the identical origin of the aminocyclitol moieties in acarbose and validamycin A, the pathways of their formation seem to be substantially different. Validamycin A formation involves a number of discrete ketocyclitol intermediates, 5‐ epi ‐valiolone, valienone, and validone, whereas no free intermediates have been identified on the pathway from 2‐ epi ‐5‐ epi ‐valiolone to the pseudodisaccharide moiety of acarbose. The stage is now set for unraveling the mechanism or mechanisms by which the two components of the pseudodisaccharide moieties of acarbose and validamycin are uniquely coupled to each other via a nitrogen bridge. © 2001 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1: 300–310, 2001