Natural products are produced by bacteria, plants, and fungi and have yielded some of the most clinically active and widely used drugs available. Several of the natural products that are produced by type II PKSs have novel scaffolds or unique rearrangements that are, in large part, due to the post PKS enzymes. Protein-protein interactions between post-PKS tailoring enzymes hamper the use of combinatorial biosynthesis in the development of novel natural product-derived drugs. Several co-dependent post-PKS enzymes have been characterized in nature, but their significance in regards to complex formation and co-dependence has been largely overlooked. Here, we report an in-depth analysis of two such post-PKS pathways, gilvocarcin and mithramycin, for which indications exist to postulate multienzyme complexes to facilitate substrate protection and channeling.
|Number of pages||12|
|State||Published - 2019|
Bibliographical noteFunding Information:
The work here summarized was supported by grants CA 091901, CA 102102, and GM 105977 of the US National Institutes of Health to J. R. We thank Professor Oleg Tsodikov for suggestions and modifications regarding several figures, and the reviewers for stimulating thoughts that were included in the discussions.
© The Royal Society of Chemistry 2019.
ASJC Scopus subject areas
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry