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Cyclization specificity in terpene synthases by residue interaction networks

Reference	BBS/E/J/000CA501
Principal Investigator / Supervisor	Dr Paul O'Maille (JIC)
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	165,167
Status	Completed
Type	Institute Project
Start date	14/01/2013
End date	13/01/2016
Duration	36 months

Abstract

Enzymes are essential to life and critical for industrial biotechnology efforts aimed at producing everyday pharmaceuticals, biofuels, and fine chemicals. A complete understanding of enzyme function will enable us to fully exploit enzymes to successfully adapt to an ever changing and uncertain world. We are continually making major strides in our understanding of enzyme function through focusing on the active site where the chemical reactions occur. However, it is well documented in directed evolution experiments that outer tier mutations (regions of the enzyme structure distant from the active site) greatly enhance catalytic activity. Although outer tiers of protein structure clearly exert profound influence on enzyme function, this remains poorly understood; our current knowledge rests largely on retrospective structure-based analysis while limited investigations have been conducted. This project seeks to deliver new fundamental knowledge into enzyme function by exploiting graph theory to identify distant residues that impact catalytic activities and establishing their linkage to the active site through residue interaction networks. Rich data sets of biochemical data, terpene products and sequences will seed computational studies to develop physical models to understand how residue interaction networks transmit mutational information through protein structure to modulate catalysis. These advances will enable formulation of general approaches for protein engineering to create libraries that are enriched with catalytically robust and functionally diverse enzymes that will ultimately reduce the resources associated with screening efforts. Developing these approaches using terpene synthase will generate novel biocatalysts for industrial biotechnology to support our growing need for therapeutics, flavors, fragrances, and other fine chemicals.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Industrial Biotechnology, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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