{Reference Type}: Journal Article
{Title}: A Fasciclin Protein Is Essential for Laccase-Mediated Selective Phenol Coupling in Sporandol Biosynthesis.
{Author}: Thiele W;Obermaier S;Müller M;
{Journal}: ACS Chem Biol
{Volume}: 15
{Issue}: 4
{Year}: 04 2020 17
{Factor}: 4.634
{DOI}: 10.1021/acschembio.0c00025
{Abstract}: The biaryl scaffold, often showing axial chirality, is a common feature of various fungal natural products. Their biosynthesis requires an oxidative phenol-coupling reaction usually catalyzed by laccases, cytochrome P450 enzymes, or peroxidases. The combination of a laccase and a fasciclin domain-containing (fas) protein is encoded in many biosynthetic gene clusters of biaryls from ascomycetes. However, such phenol-coupling systems including their regio- and stereoselectivity have not been characterized so far. Elucidating the biosynthesis of the antiparasitic binaphthalene sporandol from Chrysosporium merdarium, we demonstrate the combination of a laccase and a fas protein to be crucial for the dimerization reaction. Only the heterologous coproduction of the laccase and the fas protein led to a functional phenol-coupling system, whereas the laccase alone showed no coupling activity. Thus, the laccase/fas protein combination forms an independent group of phenol-coupling enzymes that determines the coupling activity and selectivity of the reaction concurrently and applies to the biosynthesis of many fungal natural products with a biaryl scaffold.