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Genome mining on fungal polyketide natural products for discovery of novel enzymology


Genome mining is a promising approach to elucidate the biosynthetic origins of natural products. Their structural complexity often originated from intriguing enzymatic reactions, in which understanding in biosynthesis could lead to discoveries of novel enzymology, which can be further utilized as biocatalysts for various biotechnological applications. Throughout my doctoral research, I have applied this methodology in biosynthetic studies for three fungal polyketide natural products of interest, where their synthetically challenging chemical moieties were resolved by enzyme catalysis in a highly regio- and stereospecific manner. The newly characterized enzymes have diverse functions, including isomerase, halogenase, and radical oxidase. Apart from their potential to be further developed into biocatalysts to conduct challenging chemical transformations, new drug analogs can also be developed from their bioactive parenting molecules. As a whole, this document not only aims to illustrate the theoretical and experimental details to arrive at these observations and conclusions, it can hopefully serve as motivation for future optimization and application of this promising concept of genome mining with extended applications, coupled with the rapid technological advancement.

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