Periodic Reporting for period 1 - BlueRemediomics (BlueRemediomics: Harnessing the marine microbiome for novel sustainable biogenics and ecosystem services)
Reporting period: 2022-12-01 to 2024-05-31
The recent explosion in marine microbiome research has generated extensive unassembled short-read datasets, which have limited use for biodiscovery. To overcome this, BlueRemediomics is developing a Discovery Platform that integrates informatics tools/pipelines/data (MGnify microbiome resource is the focal point) with wet-lab experimental validation. The platform employs state-of-the-art informatics tools to process short-read data into larger genomic fragments to derive metagenome assembled genomes (MAGs), generating biologically meaningful information, such as proteins, pathways, and biosynthetic gene clusters (BGCs) they encode. This facilitates analysis of a whole organism, but can also help establish synthetic communities. We aim to provide greater connectivity of this data to the marine culture collections and concomitantly develop innovative high throughput screening methods suitable for diverse use cases to enhance biodiscovery of novel products and processes of societal benefit
To evaluate platform functionality, we have chosen use cases that vary in complexity (from single enzymes to whole communities) and developmental maturity. This includes potential cosmeceutical and antimicrobial candidates produced by BGCs, while other approaches will investigate the use of fermentation extracts and products as potential phytostimulants. The project will also focus efforts on fermentation scale-up methodologies to meet evolving biotechnological demands.
In response to the EU initiative to reduce fish meal in aquaculture feeds, we will explore alternative sustainable feed sources. To address salmon survival issues when fish are transferred from controlled systems to sea cages, the project will dissect mechanisms underpinning the resilience of surviving fish by investigating whether there are specific microbiome members that confer resilience/mortality . Another approach aims to increase sustainability of the aquaculture industry by reducing fish bone waste by discovering improved bone degrading enzymes from MGnify. Similar approaches will be used to identify potential plastic degrading enzymes to address plastic pollution in the marine ecosystem. In parallel, we will investigate microbial bioremediation of UV blockers found in sunscreens, an emerging marine pollutant.
Based on the burgeoning datasets, we intend to link observations of different communities, microbes, genes, and even variants associated with ocean health or stress. The resulting Ocean Health Microbiome Index (OMHI) can potentially inform efforts to restore healthy oceans and link human activities with ocean stress. Data driven approaches will be coupled with the use of “sensor” organisms that could also represent other ecosystem monitoring services.
Underpinning BlueRemediomics is the need to improve awareness of access and benefit sharing (ABS), while ensuring the appropriate levels of intellectual property (IP) protection. By improving legal frameworks and enhancing ABS knowledge/decisions by policy stakeholders, the project aspires to sensibly balance ABS and IP obligations. Another key objective is to understand society’s appetite for biobased solutions for carbon capture, combating climate change, or using viruses to combat algal blooms in the context of the “do no significant harm” principle through Town Hall meetings.
To evaluate platform functionality, we have chosen use cases that vary in complexity (from single enzymes to whole communities) and developmental maturity. This includes potential cosmeceutical and antimicrobial candidates produced by BGCs, while other approaches will investigate the use of fermentation extracts and products as potential phytostimulants. The project will also focus efforts on fermentation scale-up methodologies to meet evolving biotechnological demands.
In response to the EU initiative to reduce fish meal in aquaculture feeds, we will explore alternative sustainable feed sources. To address salmon survival issues when fish are transferred from controlled systems to sea cages, the project will dissect mechanisms underpinning the resilience of surviving fish by investigating whether there are specific microbiome members that confer resilience/mortality . Another approach aims to increase sustainability of the aquaculture industry by reducing fish bone waste by discovering improved bone degrading enzymes from MGnify. Similar approaches will be used to identify potential plastic degrading enzymes to address plastic pollution in the marine ecosystem. In parallel, we will investigate microbial bioremediation of UV blockers found in sunscreens, an emerging marine pollutant.
Based on the burgeoning datasets, we intend to link observations of different communities, microbes, genes, and even variants associated with ocean health or stress. The resulting Ocean Health Microbiome Index (OMHI) can potentially inform efforts to restore healthy oceans and link human activities with ocean stress. Data driven approaches will be coupled with the use of “sensor” organisms that could also represent other ecosystem monitoring services.
Underpinning BlueRemediomics is the need to improve awareness of access and benefit sharing (ABS), while ensuring the appropriate levels of intellectual property (IP) protection. By improving legal frameworks and enhancing ABS knowledge/decisions by policy stakeholders, the project aspires to sensibly balance ABS and IP obligations. Another key objective is to understand society’s appetite for biobased solutions for carbon capture, combating climate change, or using viruses to combat algal blooms in the context of the “do no significant harm” principle through Town Hall meetings.
The Data Platform (MGnify) now contains 6.5K assemblies of marine metagenomics datasets which are functionally annotated, with an additional 9.8K datasets currently pending inclusion. The MGnify Genomes Marine catalogue was released, which included >50K genomes that clustered into >13K species-level clusters. A prototype of Anvi’o visualisations for MGnify eukaryotic MAGs was made available as well as an improved version of the PPanGGOLiN software for pangenome analysis using graph-based approaches. Using a combination of MAGs and isolate genomes, metabolic modelling is being conducted to develop a synthetic community for PET degradation. Over 100 sequence diverse functional families for collagenases along with 31 additional candidates are currently being analysed while 20 PETase candidates based on binding pocket structural analyses are simultaneously being synthesised for analyses. BGC predictions from MGnify using SanntiS and antiSMASH have yielded two complete clusters for cosmeceuticals (UVB absorbing MAA small molecules) with one being heterologously expressed for validation. Likewise, six carotenoid producing strains from a sponge microbiome are being assessed for pigment production. Four antimicrobial peptide candidates were shortlisted for experimental validation with plantazolicin being assessed for bioactivity. Mining MGnify provided four lanthipeptide operons which are being heterologously expressed for validation. A set of 33 marine bacterial strains are being analysed for EPS production while a tool to predict EPS BGCs is under development. A pathway to breakdown octisalate, a UV filter in sunscreens, has been identified with the current focus on identifying strains that encode this pathway for experimental validation. A list of >3.2K prokaryote culture strains from EMBRC is available, with trackers established to monitor the exchange of strains between partners and requisition of services. Efforts also covered sequencing, assembly and reconstruction of the genomes of 59 protist culture microbiomes. The computational framework has been developed to understand the distribution of autotrophic CO2 fixation beyond photosynthesis with C fixation to be studied in a model diatom. The aforementioned MAGs are also forming the foundation of the OMHI, with ML methods used to link genomes/genes to environmental stressors. MGnify is also the first ever DSI resource that provides EEZ information and ABS obligations linked with the marine sample.
Data products and novel strains are already available to BlueRemediomics partners and the wider scientific community. The data represents some of the largest collections of metagenomic assemblies, predicted proteins, and higher order functional annotations. Both the strains and data are undergoing further analyses within the project before IPR can be assessed. Since only a tiny fraction will be realistically explored within the project, efforts are underway to promote the availability of these rich resources beyond the project lifetime to maximise biodiscovery.