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SUMMARY:     Directed Evolution of Stereoselective Enzymes:   A Prolific S
 ource of Catalysts for Asymmetric Reactions
DTSTART:20131113T171500
DTEND:20131113T183000
DTSTAMP:20261005T013833Z
UID:32d2d13c5dfa5c5728843494f0535cd734422f62d920a55eac26e91f
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Dr. Dr. h.c. Manfred T. Reetz (Emeritus)\, Chemistry Dep
 artment\, Philipps-Universität\, 35032 Marburg/Germany and\nMax-Planck-In
 stitut für Kohlenforschung\, 45470 Mülheim/Germany\nEnzymes have been us
 ed as catalysts in synthetic organic chemistry and in biotechnology for a 
 long time\, but they have traditionally suffered from the following often 
 observed limitations: 1) Narrow substrate scope\; 2) Insufficient stereo- 
 or regioselectivity. During the last 15 years the methods of directed evol
 ution have eliminated these restrictions\, thereby providing a prolific an
 d inexhaustible source of catalysts for a variety of applications. It invo
 lves repeated cycles of gene mutagenesis\, expression and screening (or se
 lection). When we started our research in this area in the mid-1990s\, sev
 eral gene mutagenesis methods had already been developed by molecular biol
 ogists\, including error-prone polymerase chain reaction (epPCR)\, saturat
 ion mutagenesis and DNA shuffling\, and a few reports regarding the enhanc
 ement of enzyme stability had appeared. In contrast\, we were interested i
 n a very different catalytic parameter\, namely stereoselectivity. Early p
 roof-of-principle was delivered in 1997 using a lipase in the hydrolytic k
 inetic resolution of racemic ester\, four rounds of epPCR being employed a
 s the mutagenesis method. However\, epPCR proved not to be the optimal str
 ategy\, and therefore the combination of epPCR\, DNA shuffling and saturat
 ion mutagenesis was tested. By 2005 many academic and industrial groups ha
 d joined efforts in this new research area using these methods\, although 
 the question of efficiency was not addressed. Screening is the bottleneck 
 of directed evolution\, which means that if truly practical strategies for
  probing protein sequence space can be put into practice with generation o
 f highest-quality mutant libraries\, then the whole evolutionary process w
 ill be fast\, efficient and reliable. Our contribution in this endeavor is
  iterative saturation mutagenesis (ISM)\, which fulfills all requirements 
 for advanced directed evolution. Stereo- and regioselectivity as well as t
 he extension of substrate scope (rate) can now be achieved while minimizin
 g laboratory work. Examples pertain to the evolution of stereo- and regios
 elective enzymes such as hydrolases\, Baeyer-Villiger monooxygenases (C-C 
 activation) and P450 monooxgenases (C-H activation). Review of directed ev
 olution: Angew. Chem. Int. Ed. 2011\, 50\, 138-174\; Perspective on biocat
 alysis in organic chemistry: J. Am. Chem. Soc. 2013\; DOI: 10.1021/ja40505
 1f.
LOCATION:BCH 2218 https://plan.epfl.ch/?room==BCH%202218
STATUS:CONFIRMED
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