NUS CHEMICAL & BIOMOLECULAR Engineering


	LI, Zhi
	Associate Professor
	PhD (Org. Chem.) University of Vienna, 1991 MEng (Chem. Eng.) Chinese Academy of Forestry, Nanjing, 1985 BSc (Chem.) Nanjing University, 1982
	Contact information Blk E5, 4 Engineering Drive 4, #03-03, Singapore 117576 Tel: (65) 6516 8416 Fax: (65) 6779 1936 Email: chelz@nus.edu.sg
	Group leader (Biotech.), ETH Zurich, 1997

RESEARCH

Biocatalysis for selective and environmentally benign transformations

Biocatalysis has received increasing attention due to several distinctive features such as non-toxicity, mild reaction conditions, high chemo-, regio- and stereoselectivities, and high catalytic efficiency. It becomes a useful tool for organic synthesis, polymer synthesis, and industrial production of chemicals. It has also been recognized as an essential tool for the development of a sustainable chemical industry.

Our research interests in the area of biocatalysis focus on the development of novel enzyme catalyzed regio- and stereoselective transformations that are difficult to perform with classic chemistry, the development of efficient biocatalytic methods for enantioselective organic syntheses, the development of practical bioprocesses for the production of enantiopure pharmaceutical and agrochemical intermediates, the modification of natural products to generate new molecules with biological activities, and the use of renewable sources for the preparation of fine chemicals and fragrances.

Enantioselective reduction of ketone

Enantioselective reduction of ketone
with cofactor recycling via the coupling
of two permeabilized microorganisms

Our research work involves biocatalyst discovery by high-throughput screening of microorganisms, biocatalyst optimization by genetic and protein engineering, biotransformation with whole cells and isolated enzymes, enzyme purification, characterization, and biochemistry, enzyme catalysis in organic solvent, multi-step enzymatic reactions, cofactor recycling system, and bioprocess development. Currently, we are working on the following regio- and stereoselective reactions: hydroxylation of non-activated carbon atoms, epoxidation, trans-dihydroxylation, reduction of ketones, reductive amination, and hydrolysis of epoxides.

Microbial and synthetic biomaterials.

We are interested in preparing biodegradable and biocompatible materials from microbial origin for biomedical application. Poly-[(R)-3-hydroxyalkanoates] (PHAs) are biopolymers produced by a large variety of bacteria. The best known variants are Poly-[(R)-3-hydroxybutyrate] (PHB) and poly-[(R)-3-hydroxyoctanoate] (PHO). They are biodegradable and biocompatible materials with great application potential. However, their thermoplastic properties are rather poor: while PHB is highly crystalline and hard-brittle, PHO is weakly crystalline and soft-sticky. Our current research interest in this field is to chemically or enzymatically modify PHB and PHO as thermoplastic elastic block co-polymers.

Poly-[(R)-3-hydroxyoctanoate]
produced by Pseudomonas
oleovorans GPo1

Recently, we succeeded in preparing novel block co-polyester and co-polyesterurethane with excellent thermoplastic and mechanical properties by chemical setting of the soft PHO oligomer and hard PHB oligomer. We plan to extend our research in this direction by exploring polymer properties through changing the ratio of the hard and soft blocks, preparing block co-polyphosphate esters and co-polyorthoesters containing PHO and PHB blocks, and applying enzymes for modification and polymerization to prepare new type of polymers. These will generate biocompatible materials that could be useful for manufacturing special medical devices and drug delivery.

SELECTED PUBLICATIONS

Zhang, J.; Witholt, B.; Li, Z.*, "Coupling of permeabilized microorganisms for efficient enantioselective reduction of ketone with cofactor recycling", Chem. Commun. 2006, 398-400.

Angerer, P.; Studer, A.; Witholt, B.; Li, Z.*, "Oxidative polymerization of phenols with ion-paired horseradish peroxidase in organic solvent", Macromolecules 2005, 38, 6248-6250.

Li Z.*; Bütikofer, L.; Witholt, B, "A high-throughput measurement of enantiomeric excess of chiral alcohols by using two enzymes", Angew. Chem. 2004, 116, 1730-1734; Angew. Chem. Int. Ed. Engl. 2004, 43, 1698-1702.

Zhang, J.; Duetz, W. A.; Witholt, B.; Li, Z.*, "Fast identification of (R)- and (S)-enantioselective bacterial alcohol dehydrogenases for asymmetric reduction of ß-ketoesters", Chem. Commun. 2004, 2120-2121.

Chang, D.; Heringa, M. F.; Witholt, B.; Li, Z.*, "Enantioselective trans-dihydroxylation of non-activated C-C double bonds of aliphatic heterocycles with Sphingomonas sp. HXN-200", J. Org. Chem. 2003, 68, 8599-8606.

Andrade, A. P.; Neuenschwander, P.; Hany, R.; Egli, T.; Witholt, B.; Li, Z.*, "Synthesis and characterization of novel copolyesterurethane containing blocks of poly-[(R)-3-hydroxyoctanoate] and poly-[(R)-3-hydroxybutyrate]", Macromolecules 2002, 35, 4946-4950.

Chang, D.; Feiten, H.-J.; Engesser, K.-H.; van Beilen, J. B.; Witholt, B.; Li, Z.*, "Practical syntheses of N-substituted 3-hydroxyazetidines and 4-hydroxypiperidines by hydroxylation with Sphingomonas sp. HXN-200", Org. Lett. 2002, 4, 1859-1862.