When and why do Streptomyces make natural products?

TRUMAN_J21DTP

Bacteria have evolved the ability to produce natural products with potent bioactivities, which makes these compounds excellent candidates as medicines and agrochemicals. Streptomyces bacteria are particularly “talented” at producing specialised metabolites, including the majority of clinically used classes of antibiotics, as well as many other compounds used across medicine and agriculture. However, surprisingly little is known about when and why these molecules are made in nature. Streptomyces bacteria also have a large unrealised potential to make many more natural products than are currently known. This is due to the presence of a large number of “cryptic” biosynthetic gene clusters that have no known product.

The aim of this project is to understand the environmental conditions that trigger specialised metabolism, as well as uncovering the stimuli that enable the expression of cryptic pathways. This project will focus on plant-associated Streptomyces species, and will span microbiology, genetics, mass spectrometry, natural product chemistry and plant science. This multidisciplinary project will be based in the laboratory of Dr Andrew Truman in the Department of Molecular Microbiology at the John Innes Centre, which has world-class facilities for bacterial genetics and natural product biosynthesis. Expertise in plant-associated Streptomyces is provided by secondary supervisor Prof.

Matt Hutchings (John Innes Centre), who is an expert in studying how antibiotic-producing actinomycete bacteria help shape host associated plant microbiomes. This project provides an exciting opportunity to discover new bioactive molecules and develop skills across biology and chemistry, including the purification and structural elucidation of natural products. Applications are welcomed from students across the biological and chemical sciences who have a desire to work on a multidisciplinary project.

References:

Truman group:
Stefanato, F. L. et al. Pan-genome analysis identifies intersecting roles for Pseudomonas specialized metabolites in potato pathogen inhibition. bioRxiv DOI: 10.1101/783258 (2019).

Santos-Aberturas, J. et al. Uncovering the unexplored diversity of thioamidated ribosomal peptides in Actinobacteria using the RiPPER genome mining tool. Nucleic Acids Res. 47, 4624–4637 (2019).

Hutchings group:
Worsley, S. F. et al. Streptomyces Endophytes Promote Host Health and Enhance Growth across Plant Species. Applied and Environmental Microbiology, 86, e01053-20 (2020)