Details
| Original language | English |
|---|---|
| Pages (from-to) | 23-32 |
| Number of pages | 10 |
| Journal | Carbohydrate Research |
| Volume | 335 |
| Issue number | 1 |
| Publication status | Published - 5 Sept 2001 |
Abstract
The flexible substrate spectrum of the recombinant enzymes from the biosynthetic pathway of dTDP-β-L-rhamnose in Salmonella enterica, serovar typhimurium (LT2), was exploited for the chemoenzymatic synthesis of deoxythymidine diphosphate- (dTDP-) activated 2,6-dideoxyhexoses. The enzymatic synthesis strategy yielded dTDP-2-deoxy-α-D-glucose and dTDP-2,6-dideoxy-4-keto-α-D-glucose (13) in a 40-60 mg scale. The nucleotide deoxysugar 13 was further used for the enzymatic synthesis of dTDP-2,6-dideoxy-β-L-arabino-hexose (dTDP-β-L-olivose) (15) in a 30-mg scale. The chemical reduction of 13 gave dTDP-2,6-dideoxy-α-D-arabino-hexose (dTDP-α-D-olivose) (1) as the main isomer after product isolation in a 10-mg scale. With 13 as an important key intermediate, the in vitro characterization of enzymes involved in the biosynthesis of dTDP-activated 2,6-dideoxy-, 2,3,6-trideoxy-D- and L-hexoses can now be addressed. Most importantly, compounds 1 and 15 are donor substrates for the in vitro characterization of glycosyltransferases involved in the biosynthesis of polyketides and other antibiotic/antitumor drugs. Their synthetic access may contribute to the evaluation of the glycosylation potential of bacterial glycosyltransferases to generate hybrid antibiotics.
Keywords
- Antibiotics, dTDP-α-D-olivose, dTDP-β-L-olivose, Macrolides, Nucleotide deoxysugars
ASJC Scopus subject areas
- Chemistry(all)
- Analytical Chemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Chemistry(all)
- Organic Chemistry
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In: Carbohydrate Research, Vol. 335, No. 1, 05.09.2001, p. 23-32.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - (Chemo)enzymatic synthesis of dTDP-activated 2,6-dideoxysugars as building blocks of polyketide antibiotics
AU - Amann, Stefan
AU - Dräger, Gerald
AU - Rupprath, Carsten
AU - Kirschning, Andreas
AU - Elling, Lothar
N1 - Funding information: The authors thank Professor Dr W. Piepersberg (BUGH Wuppertal) for providing the recombinant E. coli strains expressing RmlA, RmlB, RmlC and RmlD, Dr J.C. Namyslo (TU Clausthal–Zellerfeld) for his excellent help in NMR analysis, Dr Rettberg (University Göttingen) for ESI–MS analysis. The authors thank Professor Dr P.F. Leadlay (Cambridge University) and Dr Martin Hein for critical reading of the manuscript. Financial supports by EU the grants ‘Hyglide’ (Contract No. ERBBIO 4 CT 960080) and ‘GENOVA’ (Contract No. QLK3-999-00095) to L.E. is gratefully acknowledged.
PY - 2001/9/5
Y1 - 2001/9/5
N2 - The flexible substrate spectrum of the recombinant enzymes from the biosynthetic pathway of dTDP-β-L-rhamnose in Salmonella enterica, serovar typhimurium (LT2), was exploited for the chemoenzymatic synthesis of deoxythymidine diphosphate- (dTDP-) activated 2,6-dideoxyhexoses. The enzymatic synthesis strategy yielded dTDP-2-deoxy-α-D-glucose and dTDP-2,6-dideoxy-4-keto-α-D-glucose (13) in a 40-60 mg scale. The nucleotide deoxysugar 13 was further used for the enzymatic synthesis of dTDP-2,6-dideoxy-β-L-arabino-hexose (dTDP-β-L-olivose) (15) in a 30-mg scale. The chemical reduction of 13 gave dTDP-2,6-dideoxy-α-D-arabino-hexose (dTDP-α-D-olivose) (1) as the main isomer after product isolation in a 10-mg scale. With 13 as an important key intermediate, the in vitro characterization of enzymes involved in the biosynthesis of dTDP-activated 2,6-dideoxy-, 2,3,6-trideoxy-D- and L-hexoses can now be addressed. Most importantly, compounds 1 and 15 are donor substrates for the in vitro characterization of glycosyltransferases involved in the biosynthesis of polyketides and other antibiotic/antitumor drugs. Their synthetic access may contribute to the evaluation of the glycosylation potential of bacterial glycosyltransferases to generate hybrid antibiotics.
AB - The flexible substrate spectrum of the recombinant enzymes from the biosynthetic pathway of dTDP-β-L-rhamnose in Salmonella enterica, serovar typhimurium (LT2), was exploited for the chemoenzymatic synthesis of deoxythymidine diphosphate- (dTDP-) activated 2,6-dideoxyhexoses. The enzymatic synthesis strategy yielded dTDP-2-deoxy-α-D-glucose and dTDP-2,6-dideoxy-4-keto-α-D-glucose (13) in a 40-60 mg scale. The nucleotide deoxysugar 13 was further used for the enzymatic synthesis of dTDP-2,6-dideoxy-β-L-arabino-hexose (dTDP-β-L-olivose) (15) in a 30-mg scale. The chemical reduction of 13 gave dTDP-2,6-dideoxy-α-D-arabino-hexose (dTDP-α-D-olivose) (1) as the main isomer after product isolation in a 10-mg scale. With 13 as an important key intermediate, the in vitro characterization of enzymes involved in the biosynthesis of dTDP-activated 2,6-dideoxy-, 2,3,6-trideoxy-D- and L-hexoses can now be addressed. Most importantly, compounds 1 and 15 are donor substrates for the in vitro characterization of glycosyltransferases involved in the biosynthesis of polyketides and other antibiotic/antitumor drugs. Their synthetic access may contribute to the evaluation of the glycosylation potential of bacterial glycosyltransferases to generate hybrid antibiotics.
KW - Antibiotics
KW - dTDP-α-D-olivose
KW - dTDP-β-L-olivose
KW - Macrolides
KW - Nucleotide deoxysugars
UR - http://www.scopus.com/inward/record.url?scp=0034856716&partnerID=8YFLogxK
U2 - 10.1016/S0008-6215(01)00195-1
DO - 10.1016/S0008-6215(01)00195-1
M3 - Article
C2 - 11553351
AN - SCOPUS:0034856716
VL - 335
SP - 23
EP - 32
JO - Carbohydrate Research
JF - Carbohydrate Research
SN - 0008-6215
IS - 1
ER -