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Macromolecular Structure and Function


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Simon Moore

Simon Moore

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Simon Moore's Research Interests

Synthetic biology – Small molecule biosynthesis design principles

PIs – Professor Paul Freemont, Dr Karen Polizzi and Professor Richard Kitney

DNA assembly using Golden Gate

Pathway assembly using Golden Gate

In the MSF group I will be using an holistic approach towards metabolic pathway design for the production of natural products and fine chemicals. This will use a combinatorial design approach involving the following techniques - Golden gate DNA assembly, cell-free synthetic biology, high-throughput LC-MS, protein crystallography, enzyme mechanism and microbial engineering.

Crystals and diffraction data for alkenal reductase

Semi-synthetic fragrance pathways

Investigators – Dr Simon Moore, Dr Jonek Hleba and Mr David Bell

Enzyme assay

There is clear rationale for exploring the interface between chemistry and biological transformation to provide the most simplest and direct route to product formation. Most notably this has been demonstrated with microbial production of vanillin (vanilla fragrance), artemisminin (anti-malarial drug) and semi-synthetic opiates (Hayden, 2014, Paddon et al, 2014, and Thodey et al, 2014). We are exploring the design space of natural and synthetic routes, with a focus on simplification and rapid evolvement from design to output. Currently we have identified a high-value fragrance as a potential target for this strategy. Using a custom built DNA pathway, initial testing with LC-MS has shown at least a ten-fold improvement over previous strategies. We will continue to evolve this process by investigating both natural and synthetic routes eventually providing a complete modus operandi for potential commercial exploitation.

A biosensor regulatory feedback strategy for production of optically pure D-lactate

Investigators – Dr Simon Moore and Dr Lisa Goers

Polylactic acid is a biodegradable plastic that is synthesized through chemical polymerisation using a blend of L- and D-lactate monomers for increased thermostability. The production of is D-lactate is costly in comparison to L-lactate. A number of microbial fermentation systems have recently been reported to synthesize D-lactate from inexpensive precursors (Wang et al, 2011, Desguin et al, 2014, and Gu et al, 2014). However, difficulties remain in isolating optically pure D-lactate. To challenge this aspect, we are designing a synthetic pathway to rationally produce D-lactate, whilst using a biosensing method to act as an active response system to re-route L-lactate impurities.

Other mini-projects

Combinatorial protein fusion design (with Dr. James MacDonald)

Cobalamin riboswitch engineering

Potential masters or PhD students for September 2015 entry, if you interested in any of the projects, please email me (see side panel for contact details and email) to discuss funding routes

See Simon's Google Scholar Profile