Enzymatic methylation in engineered biosynthetic pathways as a tool for product diversification Kristina Haslinger 1,2 1 Rijksuniversiteit Groningen, Chemical and Pharmaceutical Biology, Netherlands, 2 Rijksuniversiteit Groningen, Netherlands Methylation is a ubiquitous reaction in natural product biosynthesis usually occurring as a late-stage modification. Methyl groups strongly influence the bioactivity of the resulting products by altering their water solubility, membrane permeability, and stability, and by providing crucial structural features for cellular targeting. Therefore, methylation is also frequently used by medicinal chemists in the design of bioactive molecules. Compared to naturally occurring methylations it can, however, be challenging to install such methyl groups in a regioselective manner by chemical synthesis. Enzymatic methylation is an attractive tool to install methyl groups with high regioselectivity and can be used to generate precisely tailored natural and unnatural derivatives of bioactive molecules in vitro and in engineered microbes. In this talk I will present our ongoing work on identifying and applying novel oxygen-directed methyltransferases for diversifying phenylpropanoid natural products. I will discuss our recent development of a rapid in vitro screening platform for these enzymes and their use in recombinant Escherichia coli.
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© The Author(s), 2022
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