Combinatorial chemoenzymatic strategies for in vitro glycorandomization: Efforts toward antibiotic optimization

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Glycobiology

Background:

• Natural products are a rich source of drug leads, with many containing essential glycosylated structures.
• Carbohydrate moieties in drugs influence pharmacokinetics and drug-target interactions.
• Modifying glycosylation patterns on natural products presents a strategy for novel therapeutic development.

Purpose of the Study:

• To explore chemoenzymatic strategies for generating novel glycosylated natural products.
• To overcome limitations of traditional total synthesis and in vivo pathway engineering.
• To demonstrate the utility of in vitro glycorandomization (IVG) for drug discovery.

Main Methods:

• Utilizing combinatorial chemoenzymatic approaches.
• Employing in vitro glycorandomization (IVG).
• Using vancomycin as a model compound for glycorandomization.

Main Results:

• Demonstrated the effectiveness of in vitro glycorandomization (IVG).
• Showcased the potential of combining enzymatic and chemical synthesis for diversity.
• Established a method to overcome challenges in natural product drug development.

Conclusions:

• Combinatorial chemoenzymatic strategies are effective for glycorandomizing natural products.
• IVG offers an efficient approach to generate diverse glycosylated secondary metabolites.
• This strategy holds promise for the discovery of novel therapeutics.