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

Objective

"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."

Field of science

  • /natural sciences/chemical sciences/organic chemistry/amines
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

FP7-PEOPLE-2010-IIF
See other projects for this call

Funding Scheme

MC-IIF - International Incoming Fellowships (IIF)

Coordinator

JOHN INNES CENTRE
Address
Norwich Research Park Colney
NR4 7UH Norwich
United Kingdom
Activity type
Research Organisations
EU contribution
€ 201 049,60
Administrative Contact
Mary Anderson (Dr.)