Rhizomucor miehei lipase in the closed form: nucleophilic elbow = green, lid = blue-green
Candida antarctica lipase B (no lid): nucleophilic elbow = green (centre)
Current lipase OC
Epoxide hydrolase from yeasts
Reaction mechanism of epoxide hydrolase:
Present research on epoxide hydrolase Resolution of: …… as chiral building blocks for pharmaceuticals More info: dr. Carel Weijers!
Development and integration of stable aldolases in the synthesis of enantiopure functionalized nitrogen heterocycles Maud CABRIÈRES, Maurice FRANSSEN
IBOS PROJECT: 5 partners IBOS: Integration of Biosynthesis and Organic Synthesis Program Dr. Franssen/Prof. Sudhölter (Org. Chem. WU) Dr. van der Oost/Prof. de Vos (Microbiology WU) Prof. Kieboom, University of Leiden (Bio-org. Chem. UL) Prof. Rutjes, University of Nijmegen (Org. Chem. KUN) Industrial partner: DSM
General framework of IBOS project Schematic overview of the project: Final goal: integration of new generation of Aldolases in a cascade of biocatalytic conversions, aiming at the synthesis of novel nitrogen heterocyclic compounds: Aldehyde Cyanohydrin Hydroxynitrile Lyase (HNL)
C-C bond formation relevance “ Carbon- carbon bond formation lies at the heart of many organic synthesis ” Today’s fine chemistry challenge: forming building blocks with complete control of the stereochemistry of stereogenic centres Aldol reaction: one of the most powerful and famous method to enlarge carbon skeleton
Aldol condensation reaction Racemic mixture!
Aldol condensation: Nature uses aldolases Specific group of lyases, very stereoselective Nearly 30 natural aldolases identified (2000) Broad range of acceptors Stringent requirement for donors
Aldolase classification based on catalytic mechanism Type I Aldolase: –Donor activation –Imine intermediate Type II Aldolase: –Donor activation –Metal-dependent (Zn 2+ cofactor)
Aldolases from (hyper)thermophilic microorganisms Archaea and bacteria with T optimum > 80 ° C Deep sea smokers: Pyrococcus Shallow marine vents: Thermotoga (DHPS) Acidic hot spring: Sulfolobus (KDG) Volcano Themotoga Pacific Pyrococcus Yellowstone Sulfolobus
Relevant Aldolases involved in this project –KDG (2-keto-3-deoxy gluconate aldolase): –DHPS (2,3-dihydrodipicolinate synthase): –DERA (2-deoxyribose-5-phosphate aldolase):