Guest lecture: Engineering whole-cell based cascade biotransformations for enantioselective chemical synthesis

Prof. Zhi Li, Department of Chemical & Biomolecular Engineering, National University of Singapore.

31.10.2017 | Zheng Guo

Dato tor 23 nov
Tid 10:00 11:30
Sted Building 1593, room 012, iNANO

Abstract
Biocatalysis has become a useful tool for single-step enantioselective synthesis of chiral chemicals. Biocatalysis is also an attractive tool for one-pot multi-step enantioselective synthesis via cascade biotransformations, avoiding the expensive, yield-reducing, and waste-generating isolation of the intermediates in conventional multi-step synthesis. Great progress has been achieved in this field. Nevertheless, it is necessary to further develop new types of cascade biotransformations, engineer robust and efficient biocatalysis systems, and expend the scope of cascade biotransformations for practical chemical synthesis.

We recently established several new types of non-natural biocascades for enantioselective transformations, engineered recombinant Escherichia coli strains expressing the necessary enzymes as simple and active whole-cell biocatalysts for these reactions, and demonstrated the synthetic potential of the developed whole-cell based cascade biotransformations. Some representative examples will be presented: a) asymmetric trans-dihydroxylation of alkenes to 1,2-vicinal diols,[1] b) asymmetric aminohydroxylation of alkenes to 1,2-aminoalchols,[2] c) asymmetric transformation of alkenes to a-hydroxyacids,[2] d) asymmetric functionalization of alkenes to a-aminoacids,[2-3] e) enantioselective conversion of meso- or racemic epoxides to (R)-hydroxyketones,[4-5] f) enantioselective transformation of 2-alkylidenecyclopentanones to (R)-δ-Lactones or (R)-2-alkylcyclopentanones,[6-7] g) enantioselective conversion of biobased L-phenylalanine to high-value chiral chemicals,[8] h) regio- and stereoselective oxidation of alkenes to acids,[9] and i) biocatalytic formal anti-Markovnikov hydroamination and hydration of aryl alkenes.[10]

References:

[1]   Wu, S.; Chen, Y.; Xu, Y.; Li, A.; Xu, Q.; Glieder, A.; Li, Z. ACS Catal., 2014, 4, 409–420 (ACS Editors' Choice on 06 Jan 2014; featured in C&EN, 2014, 92, 8; highlighted in Synfact, 2014, 10, 0316).

[2]   Wu, S.; Zhou, Y.; Wang, T.; Too, H.-P.; Wang, D. I. C.; Li, Z. Nat. Commun., 2016, 7, 11917.

[3]   Zhou, Y.; Wu, S.; Li, Z. Adv. Synth. Catal. 2017, DOI 10.1002/adsc.201700956 (Very important publication).

[4]   Zhang, J.; Xu, T.; Li, Z. Adv. Synth. Catal. 2013, 355, 3147-3153.

[5]   Zhang, J.; Wu, S.; Wu, J. C.; Li, Z. ACS Catal.2015, 5, 51−58.

[6]   Liu, J.; Li, Z. ACS Catal. 2013, 3, 908−911.

[7]   Liu, J.; Wu, J. C.; Li, Z. Chem. Commun., 2014, 50, 9729-9732.

[8]   Zhou, Y.; Wu, S.; Li, Z. Angew. Chem. Int. Ed., 2016, 55, 11647 –11650.

[9]   Wu, S.; Zhou, Y.; Seet, D.; Li, Z. Adv. Synth. Catal. 2017, 359, 2132 – 2141 (Very Important Publication).

[10] Wu, S.; Liu, J.; Li, Z. ACS Catal. 2017, DOI: 10.1021/acscatal.7b01464.


Short Biography
Prof. Li Zhi received Ph.D. degree in organic chemistry from the University of Vienna in 1991. He then worked at the Swiss Federal Institute (ETH) Zurich as a postdoc in the Laboratory for Organic Chemistry and then as a group leader in the Institute of Biotechnology. In 2006, he moved to National University of Singapore as an associate professor at the Department of Chemical and Biomolecular Engineering. He was a fellow of the Singapore-MIT Alliance (2006–2015). His current research focuses on biocatalysis for chemical synthesis, especially for enantioselective synthesis and green pharmaceutical manufacturing; bio-based chemical and fuel production; and polymeric biomaterials. His expertise in biocatalysis includes enzyme discovery and evolution, cascade biotransformations, enzyme immobilization, biotransformations in vivo and in vitro, and bioprocess development. He received Singapore Award for Sustainable Technology from IChemE (2013) and serves as Deputy President of Singapore Catalysis Society.

Forelæsning / foredrag