... understanding life in molecular detail

Dr Ryan Seipke

Natural products; Drug discovery; Synthetic biology; Gene regulation

Our work 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.

Current major projects include:
  • Expanding the chemical space of antimycin-type depsipeptides
  • Discovery of antimycotics active against drug-resistant fungi
  • Engineering the expression of silent antibiotic biosynthetic pathways
  • Protease-mediated control of ECF RNA polymerase sigma factors

More than two-thirds of all therapeutic small molecules used in medicine are derived from or inspired by complex natural products produced by actinomycete bacteria, most notably Streptomyces spp. Our work centres on natural product discovery, understanding natural product biosynthesis and its regulation and developing synthetic biology approaches for expanding the chemical space of natural products.

Actinomycete bacteria are amazing chemical innovators and an average strain harbours 25-40 natural product biosynthetic pathways but the vast majority of these pathways are not expressed in the laboratory. A key strategy in our approach for discovering new natural products therefore focuses on activating the expression of these silent pathways by using small molecule elicitors and co-culturing techniques. We also use genome-to-molecule approaches to identify, clone and heterologously (over)express novel biosynthetic gene clusters.

A key aspect of our work is using biological systems to expand the chemical space of natural products. We are currently engineering the production of new antimycin-type depsipeptides (antimycin, neoantimycin and respirantin) for the treatment of cancer, Alzheimer’s and Parkinson’s diseases. We are also developing structure-based synthetic biology approaches to streamline engineering bespoke non-ribosomal peptide and polyketide chemical scaffolds for drug discovery.

Detailed research programme                  Close ▲

Lecturer in Bacteriology
BA (Adrian College), PhD (Cornell University)

Postdoctoral Research Fellow (Cornell University) 2008-2009
Postdoctoral Research Fellow (University of East Anglia) 2009-2013

Garstang 8.52a
School of Molecular and Cellular Biology
0113 343 35604

Selected Publications

  1. Seipke RF. 2015. Strain-level diversity of secondary metabolism in Streptomyces albus. PLoS One 10:e0116457

  2. Liu J, Zhu X, Seipke RF, Zhang W. 2015. Biosynthesis of antimycins with a reconstituted 3-formamidosalicylate pharmacophore in Escherichia coli. ACS Synth Biol, 4:559-565

  3. Seipke RF, Patrick E, Hutchings MI. 2014. Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor AntA. PeerJ 2:e253

  4. Seipke RF and Hutchings MI. 2013. The regulation and biosynthesis of antimycins. Beilstein J Org Chem 9:2556-256