Our research group is focused on advanced biocatalysis for sustainable and efficient production of chemicals, pharmaceuticals, flavor, and fragrance, and advanced polymer synthesis for the development of biodegradable and biocompatible functional materials. The main research interests are: (a) Discovery and engineering of new biocatalysts, (b) Engineering of novel and efficient biocatalytic systems, (c) Development of efficient bioprocesses, and d) Preparation of synthetic and nature polymers for biomedical application.
Some of our recent research achievements are highlighted below:
1. New biocatalysts for enantioselective transformations:
By isolation and screening of microorganisms, we discovered several powerful biocatalysts for regio- and stereo-selective hydroxylations to prepare useful and valuable enantiopure alcohols. For example, highly regio- and stereo-selective allylic hydroxylation of D-limonene was achieved with Cellulosimicrobium cellulans EB-8-4 as biocatalyst to produce natural identical (+)-trans-carveol that is a useful and valuable fragrance and flavour compound. [Wang, Z., et al, Adv. Syn. Catal. 2009, 351, 1849 –1856].
Highly enantioselective benzylic hydroxylations of benzene derivatives containing reactive functional groups were achieved for the first time with Pseudomonas monteilii TA-5 as biocatalyst, giving the corresponding (R)-benzylic alcohols in 93%-99% ee as the only product and providing with a simple access to those useful pharmaceutical intermediates. [Chen, Y., et al, Adv. Syn. Catal. 2009, in press.]
2. Tandem biocatalysts for asymmetric transformations:
The first tandem biocatalysts system for asymmetric transformations was successfully developed. By using tandem biocatalysts (one contains an enantioselective styrene monooxygenase and the other contains a regioselective epoxide hydrolase) in a two-liquid phase system for asymmetric dihydroxylation of aryl olefins, chiral aryl vicinal diols were obtained in high ee and high yield. This method provides with higher conversion and higher yield than the biotransformations in two separate steps, does no require the isolation of the epoxide intermediate, and allows for simple recovery of the diol product (aqueous phase contains only product). [Xu Y., et al, Chem. Comm., 2009, 1481-1483. This paper was selected as hot article in the webpage of ChemComm]
3. Coupled permeabilized cells for bioreduction with cofactor recycling:
An efficient cofactor recycling system for bioreduction was achieved by coupling of two permeabilized microorganisms (one contains an NADPH-dependent keto-reductase and the other contains a recombinant glucose dehydrogenase), giving 4200 times recycling of NADPH which is a very expensive co-factor required for many oxidoreductions. The permeabilized cell couple shows long-term stability and high productivity, and the high total turnover number of recycling NADPH is in the practical range for synthesizing fine chemicals. Our permeabilized cell-based approach shows several advantages over other systems. Compared with whole cells, it enables the use of externally added cofactor for efficient catalysis and cofactor recycling and allows for easy substrate access and product release. Compared with coupled isolated enzymes, permeabilized cells are cheap, easily available in large quantities, active longer, stable, and reusable. [Zhang,W. et al. Appl. Environ. Microb. 2009, 75, 687–694. This paper was one of six highlighted papers among all ASM Journals publications in March 2009 (Microbe Magazine, March 2009)]
4. Recyclable magnetic nanobiocatalyst for green oxidations:
We developed a facile synthetic method and a novel magnetic nanobiocatalyst with iron oxide core (diameter of 30 nm), polymer shell (thickness of 30 nm), and chloroperoxidase(CPO)-coated surface. The covalently bound CPO did not change the original conformation of the active site and showed the same catalytic activity and enantioselectivity as free CPO for the sulfoxidation of thioanisole to produce (R)-methyl phenyl sulfoxide in > 99% ee. The thick polymer shell significantly increased the stability of the nano-biocatalyst: no loss of the sulfoxidation activity was observed after 11 times recycling and reuse of the catalyst. Our nano-biocatalyst showed the best performance among nano-sized biocatalyst particles regarding both the retaining of free enzyme activity and the recycling of catalyst. This is also the first example of nano-biocatalyst for green oxidation, and the concept could be generally applicable for fabricating active and recyclable nano-biocatalysts. [Wang, W. et al, J. Am. Chem. Soc. 2009, 10.1021/ja905477j]
5. Three-arm shape-memory materials for biomedical application:
Novel biodegradable star poly(ester-urethanes) containing three-arm poly(e-caprolactone) (PCL) as switching segment were prepared as shape-memory polymers (SMPs) with switching temperature (Ts) around body temperature. The three-arm block co-polymer showed excellent shape-memory effect at 38 oC during cyclic thermomechanical tensile tests: shape recovery within 10s, shape fixity rate of 92%, and shape recovery rate of 99%. Such biodegradable SMPs are potentially useful as implant material in biomedical application. The invention of three-arm PCL-triols as biodegradable switching segment for the preparation of SMP solved the problem of SMPs containing linear PCL switching segment that failed to achieve shape-memory effect at body temperature. [Xue. L. et al, Macromolecules 2009, 42, 964-972]
Our research group involves in CPE program of Singapore-MIT Alliance and Joint PhD program of NUS-UIUC. We have research collaborations with Dr. Wu, J. & Dr. Zhao, H. (A*STAR-ICES), Assoc. Prof. Too, H. P. (NUS, Dept of Biochemistry), Prof. Zhao, H. (UIUC), and Prof. Wang, D. I. C.(MIT). The research works are funded by A-Star (SERC grant) and NUS (URC, FRC, Cross-Faculty, Start-up grant). Currently, 5 PhD students and 3 research fellows work in our group.