Terpenoid biocatalysis and synthetic biology

More info to follow. See and refs therein:

Currin, A. Dunstan, M.; Johannissen, L. O.; Hollywood, Katherine; Vinaixa, M.; Jervis, A.; Swainston, N.; Rattray, N. J. W.; Gardiner, J. M.; Kell, Douglas; D.; Takano, E.; Toogood, H. S.; Scrutton, N. S. "Engineering the ‘Missing Link’ in Biosynthetic (–)-Menthol Production: Bacterial Isopulegone Isomerase" ACS Catal. 2017, 8, 2012–2020. DOI: 10.1021/acscatal.7b04115

Karuppiah, V.; Ranaghan, K. E.; Leferink, N. G. H.; Johannissen, L. O.; Shanmugam, M.; Ní Cheallaigh, A.; Bennett, N. J.; Kearsey, L. J.; Takano, E.; Gardiner, J. M.; van der Kamp, M. W.; Hay, S.; Mulholland, A. J.; Leys, D.; Scrutton, N. S. “Structural Basis of Catalysis in the Bacterial Monoterpene Synthases Linalool Synthase and 1,8-Cineole Synthase.”ACS Catal. 2017, 7, 6268−6282. DOI: 10.1021/acscatal.7b01924.

Toogood, H. S.; Ní Cheallaigh, A.; Tait, S.; Mansell, D.; Jervis, A.; Lygidakis, A.; Humphreys, L.; Takano, E.; Gardiner, J. M.; Scrutton, N. S. “Enzymatic Menthol Production:  One-pot Approach Using Engineered Escherichia coli.” ACS Synthetic Biology 2015, in press DOI: 10.1021/acssynbio.5b0009

New redox biocatalysts

A collaboration with Nigel Scrutton’s lab on a BBSRC-funded programme, is aiming to develop a viable manufacturing process to exploit a wide range of novel and industrially relevant redox biotransformations. The project has identified new biocatalytic reductions and mutant enzymes with modified catalytic capabilities.

The work involves synthesis and evaluation of various potential substrates, enzymology and mechanistic investigations.

See and refs therein:

Lygidakis, A.; Ní Cheallaigh, A.; Karuppiah, V.; Hoeven, R.; Leys, D.; Gardiner, J. M.; Toogood, H. S.; Scrutton, N. S. “Pinpointing a mechanistic switch between ketoreduction and ‘ene’-reduction in short chain dehydrogenases/reductases.” 2016, 55, 9596 –9600. DOI: 10.1002/ange.201603785.

New Enzymatic Desymmetrization of Multifunctional Hindered Substrates

A powerful tactic for synthesis of enantio-enriched materials can be achieved by some enzyme classes by desymmetrizing meso or prochiral compounds.

We have identified enzymes which effect desymmetrizations on a category of novel hindered quaternary substrate, providing high yields of novel, multifunctional, enantiomerically enriched materials of >99% e.e.

We are now applying this to synthesis of novel chiral building blocks (amino acids, target N-heterocycles) as well as evaluating the full scope of the desymmetrizations on related substrates (all novel). Some molecular modelling has also been undertaken to rationalize the extraordinary selectivity observed with these substrates.

Research workers contributing to this project: Paul Mather and Stephen Super Barasa