Biomining the rumen for enzymes with industrial potential

Lead Research Organisation: Aberystwyth University
Department Name: IBERS

Abstract

The aim of this sub-programme is to utilise the vast quantities of sequencing data being produced as part of this and other projects to identify potential industrially interesting enzymes. Prospecting metagenomes for function using sequence (or catalytic domain) based similarity and/or using functional assays on metagenomic libraries allow discovery of microbial function, gene similarity/divergence, as well as allowing potential discovery of new biotechnologically useful enzymes. We will use sequence similarity and functional predictions to identify the sequences of interesting genes from the rumen. This information will be cross-referenced against meta-transcriptomic profiles generated in other projects to rank potential enzymes by their activity in real rumen environments. Finally, SNP variation analysis will be used to identify families of hydrolytic enzymes that show high levels of diversity from metagenomic datasets, and therefore may have undiscovered variants useful for industrial applications. We will work in collaboration with researchers with complimentary expertise in Bangor and within EGB ISPG to identify candidates and expedite exploitation, through site-directed mutatgenesis to test if dected variants of known hydrolytic enzymes are functional and large-scale functional profiling to identify those with the most potential for industrial use.

Publications

10 25 50
 
Description This work was a highly novel exploration of the potential of the rumen microbiota to generate compounds of industrial (particularly medical use).The work was based on screening a metagenomic library derived from the rumen microbial population, which had been previously produced through ISPG funded activity. The work was overseen primarily by Dr Sharon Huws who also supervised subject-associated PhD students (funded by Welsh Government National Research Network in Life Sciences and EU-KESS). By using a combination of practical (supervised by Dr Sharon Huws) and computational (supervised by Dr Chris Creevey) approaches a small number of candidate compounds have been identified as having potential for anti-microbial activity in a medical context. Further linkages were established with St. Georges Hospital, London for in vitro validation of efficacy. These findings are currently under consideration for potential patent.
Exploitation Route This work is being continued by Dr Huws in her new role as Reader at Queens University, Belfast.
Sectors Healthcare

 
Description This work was a highly novel exploration of the potential of the rumen to generate novel compounds of industrial (particularly medical use). There is potential for the findings to be utilised commercially subject to further efficacy/safety testing, as novel antimicrobial compounds. This contributes directly to national and international objectives to limit use of existing anti-microbials and develop new, more effective ones to decrease the risk of antimicrobial resistance.
First Year Of Impact 2017
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description KESS studentship
Amount £56,000 (GBP)
Organisation European Social Fund (Welsh Government/ EU) 
Sector Public
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description Development of novel antimicrobial therapeutics from rumen microbome. 
Organisation St George's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Our team have discovered novel putative antimicrobial peptides from the rumen microbiome through in vitro and in silico techniques. These were then passed onto our collaborators in St' George's hospital in London for testing.
Collaborator Contribution Our collaborators in St. George's hospital in London have used their expertise in synthesis of peptides and screening of therapeutically relevant organisms to identify potential novel antimicrobial componds.
Impact A series of papers/ patents on anti-microbial peptides are in process
Start Year 2016
 
Title Antibacterial Peptides. 
Description Peptides from rumen fluid with antimicrobial properties. 
IP Reference GB1621737.4 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact Nothing yet. Mouse models in progress.
 
Title Lipases, polynucleotides encoding them and their uses. 
Description Enzymatic activity from metagenomic library screening. 
IP Reference US2016060608 
Protection Patent granted
Year Protection Granted 2016
Licensed No
Impact Not yet in commercial use - research use only.
 
Description "Y Bol Buwch" (All Things Rumen) exhibit at Royal Welsh Show, July 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact • Initiated and oversaw "Y Bol Buwch" (All Things Rumen) exhibit at Royal Welsh Show, July 2015 including "Live lab" deonstrations of DNA extraction and fermentation and "Bug bashing" (type of coconut shy).
Year(s) Of Engagement Activity 2015
 
Description Visit to WHEB, EU, Brussels 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Visit of 7 researchers to Welsh Higher Education Brussels, organised by National Research network (Wales) in Low Carbon Energy and Environment. Objective was to engage with Research Programme Directors and managers of platforms related to agriculture.
Year(s) Of Engagement Activity 2016