Lipases

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Lipases
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native enzyme
R3-OH
Bi-bi ping-pong mechanism !
R1-OH
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(No Transcript)
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Esterolytic vs. lipolytic activity
Esterase activity
Lipase activity
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5
3
3
2
2
Activity
Activity
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1
0
0
1
0
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3
1
0
2
3
Substrate concentration
Substrate concentration
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Nu dus een paar dia's....
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Rhizomucor miehei lipase in the closed form
nucleophilic elbow green, lid blue-green
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Candida antarctica lipase B (no lid)
nucleophilic elbow green (centre)
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Current lipase research _at_ OC
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Epoxide hydrolase from yeasts
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Reaction mechanism of epoxide hydrolase
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Present research on epoxide hydrolase
Resolution of
as chiral building blocks for pharmaceuticals
More info dr. Carel Weijers!
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Development and integration of stable aldolases
in the synthesis of enantiopure functionalized
nitrogen heterocyclesMaud CABRIÈRES, Maurice
FRANSSEN
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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

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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
Hydroxynitrile Lyase (HNL)
Cyanohydrin
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C-C bond formation relevance

• Carbon- carbon bond formation lies at the heart
  of many organic synthesis
• Todays 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

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Aldol condensation reaction

• Racemic mixture!

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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

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Aldolase classification based on catalytic
mechanism

• Type II Aldolase
• Donor activation
• Metal-dependent (Zn2 cofactor)

• Type I Aldolase
• Donor activation
• Imine intermediate

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Aldolases from (hyper)thermophilic microorganisms

• Archaea and bacteria with Toptimum gt 80 C
• Deep sea smokers Pyrococcus
• Shallow marine vents Thermotoga (DHPS)
• Acidic hot spring Sulfolobus (KDG)

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Relevant Aldolases involved in this project

• KDG (2-keto-3-deoxy gluconate aldolase)
• DHPS (2,3-dihydrodipicolinate synthase)
• DERA (2-deoxyribose-5-phosphate aldolase)

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More information on what we do
http//www.ftns.wau.nl/oc/research/biocatalysis/bi
ocatalysis.htm