A structural and functional investigation of enzymes involved in the biosynthesis of D-tetronitrose

Full title: 

A structural and functional investigation of enzymes involved in the biosynthesis of D-tetronitrose

Author: 

Bruender, Nathan A.

Year: 

2012

Reference type: 

Thesis

ISBN/ISSN: 

9781267344489

Abstract: 

Deoxysugars are a chemically diverse group of carbohydrates derived from traditional sugars that have been modified through the removal of at least one hydroxyl group. They can differ significantly from their precursors due to various transformations leading to substantial changes in their chemical properties and functions. Deoxysugars are important components in the lipopolysaccharide of Gram-negative bacteria, the ABO antigen on red blood cells, and various therapeutic compounds, referred to as secondary metabolites, including antibiotics, antifungals, and antitumor agents.The secondary metabolites kijanimicin, produced by Actinomadura kijaniata (ATCC 31588), and tetrocarcin A, produced by Micromonospora chalcea (NRRL 11289), belong to the spirotetronate antibiotic family and exhibit both antibiotic and antitumor activities. Interestingly, the medicinal activity of tetrocarcin A is directly proportional to the number of deoxysugars decorating the metabolite. D-Tetronitrose, attached to both kijanimicin and tetrocarcin A, is an unusual nitro-containing tetradeoxysugar whose biosynthesis is likely to unveil new and exciting chemistry. In each organism, ten enzymes are required in the proposed biosynthetic pathway to convert 945;-D-glucose-1-phosphate into dTDP-D-tetronitrose. The chemistry catalyzed by the enzymes required for the fifth and sixth steps, TcaB9 and KijD3/TcaB10 respectively, in the biosynthesis are intriguing. The structural and biochemical characterization of these enzymes are the focus of this thesis.