Biosynthesis of natural products

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ABSTRACT

The reason of this study is to assess the reversibility of glycosyltransferases and to distinuish their function in the making of anticancer pharmaceutical Calicheamicin. Glycosylmoveases are enzymes that catalyze the move of a monosaccharide unit from an triggered sugar phosphate to an acceptor such as alcohol. Glycosyl transfer generally results in a monosaccharide glycoside, an oligosaccharide, or a polysaccharide. Glycosyltransferases are usually unidirectional catalysts that can catalyze the transfer of a glycosyl moiety with either a keeping or inversion configuration. It has been shown recently that Glycosyltransferases utilised in the biosynthetic pathway of Calicheamicin readily catalyzes reversible reactions that allow for: 1) The transfer of sugars from one natural backbone to the next, 2) the exchange of native natural glycosides with exogenous carbohydrates, and 3) the synthesis of bizare NDP-sugars from glycosylated products. The freshly found reversibility of Glycosyltransferases permits for a simpler way of conceiving Calicheamicins thus enhancing its presentation and also, allowing for production of better accomplishing Calicheamicin variants.

CONTENTS

ABSTRACT2

INTRODUCTION4

Coenzymes Engaged In Dopamine Biosynthesis9

History and structure of Calicheamicin15

LITERATURE REVIEW18

The synthesis of bizare NDP-sugars18

The exchange of native natural-product glycosides19

The move of a sugar from one natural product backbone24

The checking of reversibility on other GT systems26

METHODOLOGY29

MOLECULAR MODELS IN CATAGORIES29

REFERENCES43

INTRODUCTION

Glycosylation is the process of adding saccharides to proteins and lipids utilising distinct and exact glycosyltransferases (GT). This is one of the most significant methods engaged in the synthesis of membrane and secreted proteins. Glycosylation is an enzyme administered method of two kinds: N-linked glycosylation to the amide nitrogen of asparagines edge chains and O-linked glycosylation to the hydroxyl oxygen of serine and thereonine edge chains.¹ N-linked glycosylation occurs in the Endoplasmic Reticulum (ER), can be continued in the Golgi Apparatus (GA) and the process is initiated first with a lipid-linked oligosaccharide precursor being synthesized (Figure 1). (Baianu, I. 1970)

Figure 1. Synthetic thinking of Lipid-linked Oligosaccharide Precursor. (Baianu, I. 1970)

The precursor oligosaccharide is attached by a pyrophosphoryl assembly to dolichol. It is a long (75-95 carbon atoms), majorly hydrophobic polyisoprenoid lipid (Figure 2):

Figure 2. Structure of the Dol-P lipid utilised in assembling the dolichol oligosaccharide forerunner in N-linked oligosaccharide biosynthesis. The number of isoprene does again (n) varies between 15 and 19.1;

Dolichol is localized on the uneven ER and the biosynthesis begins at the cytosolic face of the ER. The process starts with 2 GlcNAc and 5 mannose residues being added one at time to dolichol phosphate. Then it is flipped and moved to the growing oligosaccharide. The carrier is then flipped back afresh to the cytosolic face. Once this is finished, the oligosaccharide forerunner is transferred from the dolichol to an Asn residue on the nascent polypeptide. Because of this method, glycosylation is glimpsed as happening cotranslationally. The Asn residue must be in a sequence N-X-S/T where X cannot be Pro or Asp 2 .The method is catalyzed by oligosaccharide protein transferase which is made up of three subunits: two of them are ribophorins - ER transmembrane proteins and the third subunit has the catalytic ...