Chemoenzymatic synthesis of UDP-glucose for trehalose analogue production
Document Type
Event
Faculty Mentor
Peter Woodruff
Abstract
Worldwide, Mycobacterium tuberculosis remains a significant health problem, taking more than a million lives a year. With the rise of antibiotic-resistant strains, developing new treatments is important. Tuberculosis utilizes multiple pathways to make trehalose, a sugar made of two glucose molecules. As a result, analogues of trehalose have been an important tool for investigating the disease and its metabolic pathways. Evidence has also shown that some trehalose analogues have antimicrobial activity. Analogues are difficult to synthesize chemically, but they can be produced more effectively with enzymes. Previously, studies demonstrated that the enzyme TreT converted glucose analogues and UDP-glucose into trehalose analogues in about an hour. However, UDP-glucose is expensive; thus, utilizing chemoenzymatic synthesis to produce UDP-glucose is important to increasing accessibility. UDP-glucose can be made using enzymes phosphoglucomutase (PGM) and UDP-glucose pyrophosphorylase (GalU). Each of the enzymes were expressed, and trehalose analogues were synthesized successfully when combined with TreT in a one-pot reaction.
Chemoenzymatic synthesis of UDP-glucose for trehalose analogue production
Worldwide, Mycobacterium tuberculosis remains a significant health problem, taking more than a million lives a year. With the rise of antibiotic-resistant strains, developing new treatments is important. Tuberculosis utilizes multiple pathways to make trehalose, a sugar made of two glucose molecules. As a result, analogues of trehalose have been an important tool for investigating the disease and its metabolic pathways. Evidence has also shown that some trehalose analogues have antimicrobial activity. Analogues are difficult to synthesize chemically, but they can be produced more effectively with enzymes. Previously, studies demonstrated that the enzyme TreT converted glucose analogues and UDP-glucose into trehalose analogues in about an hour. However, UDP-glucose is expensive; thus, utilizing chemoenzymatic synthesis to produce UDP-glucose is important to increasing accessibility. UDP-glucose can be made using enzymes phosphoglucomutase (PGM) and UDP-glucose pyrophosphorylase (GalU). Each of the enzymes were expressed, and trehalose analogues were synthesized successfully when combined with TreT in a one-pot reaction.
