Microbial natural products have diverse chemical structures and bioactivities, which range from cell-cell signalling, nutrient acquisition, antibiotic activity to stress resistance (1). The diverse bioactivity of natural products enables them to drive the chemical interactions between microbes and shape microbial communities. Natural products are synthesized by multi-enzyme biosynthetic machineries, referred to as biosynthetic gene clusters (BGCs) or cryptic BGCs if their associated natural products are unknown (2).

Hypothesis: P. aeruginosa produces natural products encoded by cryptic BGCs that play important roles in chemical interaction and bacterial physiology. 

Objectives: 1) Determine the most favourable conditions for natural product biosynthesis by cryptic BGCs with bacterial reporter strains. 2) Identify the synthesized natural products and elucidate their structures. 3) Characterize their bioactivity and determine their role in chemical interaction and the physiology of the producing organism.

1.            Gulick AM. Nonribosomal peptide synthetase biosynthetic clusters of ESKAPE pathogens. Nat Prod Rep 34, 981-1009 (2017).

2.            Covington BC, Xu F, Seyedsayamdost MR. A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters. Annu Rev Biochem 90, 763-788 (2021).

Techniques: The student will receive training in microbiology, molecular biology, chemical biology (mass spectrometry) and data analysis. Specifically, training in chemical biology will encompass metabolite extraction, sample processing, data analysis and molecular networking. Training in microbiology and molecular biology includes the generation of bacterial reporter strains and mutants and different bacterial culturing techniques.