Accelerating the biotechnological potential of marine microalgae using a molecular networking comparative metabolomics approach (PHYCONET round 4 PoC)

Often bacteria, especially the order actinomycetales are investigated for new drugs as they account for the production of over 45% of all bioactive microbial metabolites. Despite research into the biofuel potential of algal strains, the secondary metabolite potential of marine microalgae for novel antibiotics to combat antibiotic resistance is yet to be systematically investigated. Genome sequencing of microalgal strains has revealed that even well studied species (in terms of biofuels and primary metabolites) have the genetic potential to produce a wealth of secondary or specialized metabolites than discoveries to date would suggest. While this revelation has generated interest in the field of algal natural product discovery, there remains inefficiencies in the processes by which known natural products are detected and new compounds prioritized for isolation, structure elucidation and industrial bioprocessing. Taxonomically characterized strains will be fermented to induce chemically diverse metabolites from each strain. Through already developed protocols, the algal metabolites will be extracted using adsorbant resin, and metabolite profiles for each crude extract will be generated using Liquid Chromatography High Resolution Mass Spectrometry (LC-HRMS). The extracts will be further investigated using tandem mass spectrometry (HR-MS/MS) to generate fragmentation data of each parent ion in the crude extract. This HR-MS/MS data will be used to create a molecular network using Global Natural Products Social Molecular Networking. This will allow comparison of complex microalgal crude extracts based on similarities and differences of metabolite fragmentation across multiple strains (up to hundreds). This cutting-edge approach to chemical dereplication allows identification of known metabolites in addition to analogues of known chemicals and thus rapidly identifies areas of unique (to for example a particular strain) chemistry for isolation and chemical prioritization. Novel chemistry identified using this innovative dereplication strategy allows for streamlined antibiotic assay prioritisation and accelerates commercial targets for the IB sector based on chemical structural class information. Using this innovative approach will allow the unprecedented biological diversity of marine microalgae to be investigated as an exciting resource of chemical diversity across taxonomic and phylogenetic boundaries for biomedical applications in the comparative metabolomics era.