Enzymatic studies on aromatic prenyltransferases

Area of Science:

• Biochemistry
• Natural Product Chemistry
• Enzyme Engineering

Background:

• Aromatic prenyltransferases (PTases), encompassing ABBA-type and dimethylallyl tryptophan synthase (DMATS)-type enzymes from microbial sources, are crucial for natural product diversification.
• These enzymes facilitate the synthesis of prenylated compounds, which often exhibit enhanced biological activities.
• Significant progress has been made in characterizing these PTases and utilizing them for enzymatic synthesis over the past decade.

Purpose of the Study:

• To highlight recent advancements in the chemoenzymatic synthesis of unnatural prenylated compounds.
• To showcase examples of enzyme engineering applied to ABBA-type and DMATS-type PTases.
• To underscore the potential of engineered PTases in expanding the chemical diversity of natural products.

Main Methods:

• Characterization of microbial ABBA-type and DMATS-type prenyltransferases.
• Development of chemoenzymatic strategies for synthesizing prenylated molecules.
• Enzyme engineering techniques to modify PTase activity and substrate specificity.

Main Results:

• Demonstration of successful chemoenzymatic synthesis of novel prenylated compounds using PTases.
• Identification of engineered PTases with altered or improved catalytic properties.
• Expansion of the repertoire of accessible prenylated natural product analogs.

Conclusions:

• Engineered aromatic prenyltransferases offer powerful tools for generating diverse and potentially bioactive prenylated compounds.
• Chemoenzymatic synthesis combined with enzyme engineering provides a versatile platform for accessing unnatural natural products.
• Further exploration of PTase engineering holds promise for drug discovery and biotechnology.