New antimycotics

This project takes advantage of our actinomycete culture collection which includes many insect-associated actinomycetes. We use chemical elicitors to switch on expression of silent biosynthetic gene clusters and identify novel antimycotic agents by screening for activity against the multidrug resistant fungal pathogen Scedosporium prolificans. This project is currently funded by The British Society for Antimicrobial Chemotherapy (GA2014_006P).

From genomes to molecules

This project uses genome sequencing and advanced bioinformatics approaches to link natural products with their biosynthetic pathways and facilitate identification of novel small molecule therapeutics. The ultimate aim of this project is to clone, heterologously (over)express and bioengineer complex natural products. This project is funded by The Royal Society (RG140011).

 Research

Research in the Seipke Lab centres on complex natural products produced by actinomycete bacteria. We use genome-to-molecule approaches to guide the discovery of novel molecules and to link biosynthetic pathways to known compounds. Our driving aspiration is to develop structure-based synthetic biology approaches to expand the chemical diversity of proven therapeutics and to bioengineer the production of novel chemical scaffolds. Our work is currently funded by the University of Leeds, The British Society for Antimicrobial Chemotherapy and The Royal Society.

Research

Antimycin-type depsipeptides comprise a large family of secondary metabolites produced by actinomycete bacteria. Key members of this family include antimycin (9-membered ring) and neoantimycin (15-membered ring). These compounds have diverse targets and tremendous therapeutic potential for the treatment of cancer. Antimycin-type depsipeptides show clear evidence of shared evolutionary history. While synthetic biologists and bioengineers have yet to master combinatorial biosynthesis, nature has long used this technique to engineer ring expansion in antimycin-type depsipeptides, as well as a high degree of promiscuity in the selection of building block monomers; these features make them ideal candidates for rational drug design. This project aims to both bioengineer the production of new antimycin-type depsipeptides using synthetic biology and to understand the structural biology of interaction with their targets.

© Copyright Ryan F. Seipke and Jayne L. Gifford

New antimycin-type depsipeptides

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