Biaryl-Forming Enzymes from Aspergilli Exhibit Substrate-Dependent Stereoselectivity

Area of Science:

• Biochemistry
• Molecular Biology
• Mycology

Background:

• Natural biaryls are usually found as single isomers within organisms.
• The biosynthesis of complex natural products often involves intricate enzymatic pathways.

Purpose of the Study:

• To identify the biosynthetic genes responsible for producing aurasperone- and bifonsecin-type biaryls in Aspergillus species.
• To characterize the enzymes involved in naphthopyrone monomer dimerization.

Main Methods:

• Bioinformatic analysis to identify gene clusters.
• Gene expression studies in Aspergillus species.
• Enzymatic assays using purified cytochrome P450 enzymes.

Main Results:

• Identification of a separate gene cluster for tailoring enzymes, distinct from the polyketide synthase gene.
• Discovery of a novel subfamily of cytochrome P450 enzymes catalyzing naphthopyrone monomer dimerization.
• Demonstration that enzyme stereoselectivity is substrate-dependent, leading to pure or mixed enantiomers.

Conclusions:

• The biosynthesis of aurasperone- and bifonsecin-type biaryls involves a unique set of tailoring enzymes and cytochrome P450s.
• Substrate-specific stereoselectivity in dimerization offers insights into controlling natural product isomer formation.