Combinatorial Biocatalytic Synthesis of New Resorcylic Acid Lactones

Microorganisms are a rich source of enzymes for structural modification. As a result, microorganisms are extensively used in biotransformation of various natural products. Based on our recent work on biotransformation of aromatic molecules by Beauveria bassiana and reconstitution of a novel fungal halogenase Rdc2 in Escherichia coli, we designed a sequential biotransformation process by combining the bacterial and fungal catalytic steps. A natural resorcylic acid lactone, dihydroresorcylide, was used as the substrate. Through this biocatalytic process, we were able to synthesize a novel chlorinated and glycosylated derivative of dihydroresorcylide, thus providing a new combinatorial biocatalytic approach to preparing “unnatural” natural products.