Tailoring enzyme strategies and functional groups in biosynthetic pathways

Area of Science:

• Biochemistry
• Organic Chemistry
• Metabolic Engineering

Background:

• Secondary metabolites are complex molecules derived from primary metabolic pathways.
• Enzymatic tailoring is crucial for increasing the structural and functional diversity of metabolites.

Purpose of the Study:

• To review the chemical strategies employed by tailoring enzymes in metabolite scaffold maturation.
• To categorize enzyme strategies based on their oxidative or nonoxidative mechanisms.

Main Methods:

• Literature review of enzymatic tailoring strategies from 2000 to 2022.
• Analysis of functional group transformations and enzyme mechanisms.

Main Results:

• Nonoxidative enzymes transfer activated fragments (acyl, alkyl, glycosyl).
• Oxidative enzymes include oxygen-independent (redox catalysts) and oxygen-dependent (mono- and dioxygenases) types.
• Oxygen-dependent enzymes generate radical species at sp3 and sp2 carbons, enabling diverse modifications.

Conclusions:

• Enzymatic tailoring employs distinct chemical strategies to build complex metabolite scaffolds.
• Understanding these strategies is key to metabolic engineering and natural product synthesis.