O-methyltransferases selectively modify anthraquinone natural products

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Aromatic polyketides, such as anthraquinone AQ-256, are produced by various microorganisms.
• O-methyltransferases (OMTs) are enzymes involved in the methylation of diverse natural products.
• Understanding the enzymatic pathways for polyketide modification is crucial for natural product biosynthesis.

Purpose of the Study:

• To identify and characterize O-methyltransferases involved in the biosynthesis of anthraquinone AQ-256.
• To elucidate the structural basis for the substrate specificity and catalytic mechanism of these OMTs.
• To provide insights into the sequential methylation process of AQ-256.

Main Methods:

• Enzyme identification and purification from Gram-negative bacteria.
• Co-crystal structure determination of OMTs with AQ-256 and its derivatives using X-ray crystallography.
• Enzymatic assays to confirm methylation activity and product formation.

Main Results:

• Five O-methyltransferases were identified.
• Three of these OMTs were shown to catalyze the sequential methylation of AQ-256.
• Co-crystal structures revealed the active site architecture and substrate binding modes, explaining enzyme specificity.

Conclusions:

• The study elucidates a novel enzymatic pathway for the sequential methylation of anthraquinone AQ-256.
• Structural insights into the OMTs provide a molecular understanding of substrate recognition and catalysis.
• This work contributes to the field of natural product biosynthesis and enzyme engineering.