Terminal alkyne is a readily derivatized functionality commonly used in organic synthesis, pharmaceutical science, and bioorthogonal chemistry. This functionality is also found in various natural products, but the underlying biosynthetic pathways often remain elusive. We recently characterized a few carrier protein-dependent terminal alkyne biosynthetic machinery in microbes. We further demonstrated that these enzymatic machinery can be exploited for the <i>in situ</i> generation and incorporation of terminal alkynes into various natural product scaffolds. These results highlight the prospect for tagging major classes of natural products, including polyketides and polyketide/non-ribosomal peptide hybrids, using synthetic biology. Coupling with diverse azido analytical handles, our work enables the visualization, enrichment, quantification, diversification, and mode of action study of natural products through bioorthogonal chemistry. For example, using a fluorogenic probe, a natural product-based, quantitative, high-throughput screening method was established, serving as a useful tool for evolving natural product biosynthetic enzymes that can efficiently function in specific pathways to produce natural product analogues in high titers.

Engineered biosynthesis of terminal alkyne-tagged natural products

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.