Award details

Quantitative exploration of catalytic landscapes underlying the functional divergence of triterpene synthases

Reference	BBS/E/J/000CA446
Principal Investigator / Supervisor	Professor Anne Osbourn
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	54,154
Status	Completed
Type	Institute Project
Start date	19/09/2011
End date	18/09/2013
Duration	24 months

Abstract

Plants have evolved the ability to produce diverse terpenes to communicate, thrive and survive in various ecologies and these have profound benefits for humanity as therapeutics and bioactive compounds. While chemical novelty has contributed to the success of sessile organisms like plants, the evolutionary origins of terepene complexity are poorly understood at the molecular level. Among terpenes, triterpenes are produced by oxidosqualene cyclase (OSC’s) family members. In OSC family, beta-amyrin synthases (BAS) is involved in triterpene secondary metabolism and functionally diverged from but is closely related to cycloartenol synthases (CAS) of sterol primary metabolism. Structural changes that interconnect this pair of enzymes remain unknown and hence form a prime model system to address many basic questions; what are/were the key structural changes responsible for the conversion of CAS to BAS?Is this transition unique or a recurring theme? How has this functional transition occurred in other CAS contexts? To approach these questions, project quantitatively explores catalytic landscape subtended by extant CA and BA synthases of plants. Catalytic landscaping is a novel concept that uses multidisciplinary approaches to discern the structural changes that interconnect a pair of recently diverging enzymes. Elucidating the catalytic landscape of CAS and BAS would yield important insights into the evolution of triterpene complexity as a whole and aid applied efforts to engineer pathways for novel triterpenes. Project aims to; i)computational and structural modelling of CAS and BAS to identify functionally relevant amino acids to enable ii)in silico design and synthesis of mutant library in CA background using structure-based combinatorial protein engineering. Library will be iii) expressed in yeast to identify and quantify triterpenes using GC-MS. iv)analysis of data to build models to relate changes in product specificity to the underlying structural changes in CAS-BAS.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Industrial Biotechnology, Microbiology, Plant Science, 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

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search