Highly regio- and enantioselective multiple oxy- and amino-functionalizations of alkenes by modular cascade biocatalysis.
New types of asymmetric functionalizations of alkenes are highly desirable for chemical synthesis. Here, we develop three novel types of regio- and enantioselective multiple oxy- and amino-functionalizations of terminal alkenes via cascade biocatalysis to produce chiral α-hydroxy acids, 1,2-amino alcohols and α-amino acids, respectively. Basic enzyme modules 1-4 are developed to convert alkenes to (S)-1,2-diols, (S)-1,2-diols to (S)-α-hydroxyacids, (S)-1,2-diols to (S)-aminoalcohols and (S)-α-hydroxyacids to (S)-α-aminoacids, respectively. Engineering of enzyme modules 1 &2, 1 &3 and 1, 2 &4 in Escherichia coli affords three biocatalysts over-expressing 4-8 enzymes for one-pot conversion of styrenes to the corresponding (S)-α-hydroxyacids, (S)-aminoalcohols and (S)-α-aminoacids in high e.e. and high yields, respectively. The new types of asymmetric alkene functionalizations provide green, safe and useful alternatives to the chemical syntheses of these compounds. The modular approach for engineering multi-step cascade biocatalysis is useful for developing other new types of one-pot biotransformations for chemical synthesis.
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.|Singapore-MIT Alliance, National University of Singapore, Singapore 117583, Singapore.|Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
Shuke
S
Wu
Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
Yi
Y
Zhou
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.
Tianwen
T
Wang
Singapore-MIT Alliance, National University of Singapore, Singapore 117583, Singapore.
Heng-Phon
HP
Too
Singapore-MIT Alliance, National University of Singapore, Singapore 117583, Singapore.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Daniel I C
DI
Wang
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.|Singapore-MIT Alliance, National University of Singapore, Singapore 117583, Singapore.|Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
Zhi
Z
Li
D000475:Alkenes / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D000605:Amino Alcohols / Q000737:chemistry*; D055162:Biocatalysis; D004926:Escherichia coli / Q000737:chemistry* / Q000201:enzymology; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism; D013343:Styrenes / Q000737:chemistry
D000475:Alkenes; D000596:Amino Acids; D000605:Amino Alcohols; D013343:Styrenes