An Enzyme Module System for the Synthesis of dTDP‐activated Deoxysugars from dTMP and Sucrose

ChemBioChem
2005.0

Abstract

<jats:title>Abstract</jats:title><jats:p><jats:italic>A flexible enzyme module system is presented that allows preparative access to important dTDP‐activated deoxyhexoses from dTMP and sucrose. The strategic combination of the recombinant enzymes dTMP‐kinase and sucrose synthase (SuSy), and the enzymes RmlB (4,6‐dehydratase), RmlC (3,5‐epimerase) and RmlD (4‐ketoreductase) from the biosynthetic pathway of dTDP‐β‐<jats:sc>L</jats:sc>‐rhamnose was optimized. The SuSy module (dTMP‐kinase, SuSy, ±RmlB) yielded the precursor dTDP‐α‐<jats:sc>D</jats:sc>‐glucose (<jats:bold>2</jats:bold>) or the biosynthetic intermediate dTDP‐6‐deoxy‐4‐keto‐α‐<jats:sc>D</jats:sc>‐glucose (<jats:bold>3</jats:bold>) on a 0.2–0.6 g scale with overall yields of 62 % and 72 %, respectively. A two‐step strategy in which the SuSy module was followed by the deoxysugar module (RmlC and RmlD) resulted in the synthesis of dTDP‐β‐<jats:sc>L</jats:sc>‐rhamnose (<jats:bold>4</jats:bold>; 24.1 μmol, overall yield: 35.9 %). Substitution of RmlC by DnmU from the dTDP‐β‐<jats:sc>L</jats:sc>‐daunosamine pathway of</jats:italic> Streptomyces peucetius <jats:italic>in this module demonstrated that DnmU acts in vitro as a 3,5‐epimerase with <jats:bold>3</jats:bold> as substrate to yield <jats:bold>4</jats:bold> (32.2 μmol, overall yield: 44.7 %). Chemical reduction of <jats:bold>3</jats:bold> with NaBH<jats:sub>4</jats:sub> gave a mixture of the C‐4 epimers dTDP‐α‐<jats:sc>D</jats:sc>‐quinovose (<jats:bold>6</jats:bold>) and dTDP‐α‐<jats:sc>D</jats:sc>‐fucose (<jats:bold>7</jats:bold>) in a ratio of 2:1. In summary, the modular character of the presented enzyme system provides valuable compounds for the biochemical characterization of deoxysugar pathways playing a major role in microbial producers of antibiotic and antitumour agents.</jats:italic>

Knowledge Graph

Similar Paper

An Enzyme Module System for the Synthesis of dTDP‐activated Deoxysugars from dTMP and Sucrose
ChemBioChem 2005.0
Precursor for biosynthesis of sugar moiety of doxorubicin depends on rhamnose biosynthetic pathway in Streptomyces peucetius ATCC 27952
Applied Microbiology and Biotechnology 2010.0
A Bifunctional 3,5-Epimerase/4-Keto Reductase for Nucleotide-Rhamnose Synthesis in Arabidopsis
Plant Physiology 2004.0
Exploration of two epimerase homologs in Streptomyces peucetius ATCC 27952
Applied Microbiology and Biotechnology 2013.0
Exploration of two epimerase homologs in Streptomyces peucetius ATCC 27952
Applied Microbiology and Biotechnology 2013.0
Characterization of TDP-4-Keto-6-deoxy-<scp>d</scp>-glucose-3,4-ketoisomerase from the <scp>d</scp>-Mycaminose Biosynthetic Pathway of <i>Streptomyces fradiae</i>:  In Vitro Activity and Substrate Specificity Studies
Biochemistry 2007.0
Enzymatic Conversion of Glucose to UDP-4-Keto-6-Deoxyglucose in <i>Streptomyces</i> spp
Applied and Environmental Microbiology 1998.0
Glucose is a Precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus
Tetrahedron 1992.0
An efficient approach for cloning the dNDP-glucose synthase gene from actinomycetes and its application in<i>Streptomyces spectabilis</i>, a spectinomycin producer
FEMS Microbiology Letters 2000.0
Development of a Streptomyces venezuelae-Based Combinatorial Biosynthetic System for the Production of Glycosylated Derivatives of Doxorubicin and Its Biosynthetic Intermediates
Applied and Environmental Microbiology 2011.0