Chapter 12. The power of glycosyltransferases to generate bioactive natural compounds.
Glycosyltransferases (GTs), which catalyze the attachment of a sugar moiety to an aglycone are key enzymes for the biosynthesis of many valuable natural products. Their use in pharmaceutical biotechnology is becoming more and more visible. The promiscuity of GTs has prompted efforts to modify sugar structures and alter the glycosylation patterns of natural products. Here, we present the state of the art in this field. After describing the importance of GTs in determining the functions of natural products, a general survey of glycosyltransferase-catalyzed reactions is documented. This is followed by an overview of crystallized GT-B superfamily members and a discussion of the amino acids of these GTs involved in substrate binding. The main chapter is concerned with emphasizing the application of GTs in metabolic pathway engineering leading to novel unnatural bioactive compounds. A strategy to explore new GTs is presented as well as strategies to generate artificial GTs either randomly or in a rational design.
Institut für Pharmazeutische Wissenschaften, Lehrstuhl für Pharmazeutische Biologie und Biotechnologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Johannes
J
Härle
Andreas
A
Bechthold
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000096:biosynthesis* / Q000737:chemistry; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D013379:Substrate Specificity
D001426:Bacterial Proteins; D001688:Biological Products; D016695:Glycosyltransferases