This project proposes to clone and express two lipases from Pseudomonas reinekei (PRL) and Pseudomonas brenneri (PRB) and explore their applications in organic synthesis. These enzymes were recently identified by screening of soil samples to be of interest as biocatalysts. Preliminary work suggests these enzymes are particularly robust and “promiscuous”. We have previously employed lipases in synthesis of sugar esters and flavour compounds [Dheeman, 2010] and we are interested in the application of these methodologies to synthesis of lipopeptides and liponucleotides. Lipopeptides are known for their action as antibacterial agents and more recently as potent anti-cancer compounds [Chauhan, 2020]. They are also effective in bioremediation applications as biosurfactants. Liponucleotides have been shown to dramatically alleviate the symptoms associated with Flu and Covid 19 [Rosas, 2021]. Synthesis of these compounds will be used as demonstration projects.
The ability of these enzymes to synthesis fatty acid sugar esters will be evaluated as initial step to explore substrate specificity of these new enzymes.
Skill-sets: Cloning and expressing lipases; Computational modelling; Synthesis.
Chauhan V, Kanwar SS. Lipopeptide(s) associated with human microbiome as potent cancer drug. Semin Cancer Biol. 2021 May;70:128-133. doi: 10.1016/j.semcancer.2020.06.012. Epub 2020 Jun 20. PMID: 32574814
Dheeman DS, Henehan GT, Frías JM. Purification and properties of Amycolatopsis mediterranei DSM 43304 lipase and its potential in flavour ester synthesis. Bioresour Technol. 2011 Feb;102(3):3373-9. doi: 10.1016/j.biortech.2010.11.074. Epub 2010 Nov 21. PMID: 21145735.
Rosas LE, Doolittle LM, Joseph LM, El-Musa H, Novotny MV, Hickman-Davis JM, Hite RD, Davis IC. Post-exposure Liponucleotide Prophylaxis and Treatment Attenuates ARDS in Influenza-infected Mice. Am J Respir Cell Mol Biol. 2021 Feb 19. doi: 10.1165/rcmb.2020-0465OC. Epub ahead of print. PMID: 33606602.
Student requirements for this project
min. 2.1 BSc in a Biological Science
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