Regio- and stereoselective intermolecular oxidative phenol coupling in Streptomyces

Area of Science:

• Biochemistry
• Microbiology
• Natural Product Biosynthesis

Background:

• Intermolecular oxidative phenol coupling is crucial for forming atroposelective biaryl compounds in nature.
• While well-understood in plants and fungi, the bacterial mechanisms for this dimerization remain largely unknown.
• Julichromes, spectomycins, and setomimycin are bacterial biaryl natural products with poorly understood biosynthetic pathways.

Purpose of the Study:

• To investigate the biosynthesis of julichromes, spectomycins, and setomimycin in streptomycetes.
• To elucidate the mechanism of regioselective biaryl compound formation from a common polyketide precursor.
• To identify the enzymes responsible for the dimerization of polyketide monomers in bacteria.

Main Methods:

• Genome analysis of relevant streptomycete strains.
• Construction and analysis of gene deletion mutants.
• Biochemical characterization of involved enzymes.

Main Results:

• Biosynthetic gene clusters for julichromes, spectomycins, and setomimycin were identified.
• The regioselectivity of the coupling reaction was found to be strain-dependent.
• Cytochrome P450 enzymes were confirmed to be essential for the dimerization of polyketide monomers.

Conclusions:

• Cytochrome P450 enzymes play a fundamental role in the oxidative phenol coupling and dimerization of polyketide precursors in streptomycetes.
• This study clarifies the poorly understood bacterial biosynthesis of complex biaryl natural products.
• The findings provide insights into the evolution and diversity of natural product biosynthesis in bacteria.