Soil bacteria make compounds called anthracyclinones (ACs), some of which have powerful therapeutic activity. ACs have complicated structures that are produced by enzymes found in the bacteria. This project will “mix-and-match†these enzymes to make novel ACs expected to have antibiotic and anticancer activity. As a Research in Undergraduate Institutions (RUI) project, it will attract undergraduate students to careers in science and engineering by involving them in the completion of the research aims. The professor and students will communicate to the public through a podcast.
The overall objective of the project is to characterize polyketide synthase (PKS) genetic parts. These parts will be brought together in a platform (BIOPOLYMER) to form productive in vivo biosynthetic pathways. BIOPOLYMER will facilitate rational combinatorial biosynthesis. The central hypothesis is that combinatorial biosynthesis of selected PKS and post-PKS enzymes will facilitate the production of rationally designed anthracyclinones. The hypothesis will be tested in two specific aims: (1) characterize and develop PKS BioBricks parts for metabolic engineering of tricyclic anthracyclinones via heterologous expression of these components in actinomycetes; (2) characterize and develop post-PKS BioBricks parts for metabolic engineering of tetracyclic and oxidatively modified anthracyclinones in actinomycetes. At the completion of these studies, PKS and post-PKS gene sets will be identified that compose “new-to-nature†biosynthetic pathways for synthesizing new pharmaceuticals or commodity chemicals. The strains and vectors that are developed in this project period will be shared with the broader natural products community.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
