Abstract
Biocatalytic cascade conversion of racemic amines into optically pure ones using enantiocomplementary ω-transaminases (ω-TAs) has been developed by thermodynamic and kinetic control of reaction pathways where 12 competing reactions occur with pyruvate and isopropylamine used as cosubstrates. Thermodynamic control was achieved under reduced pressure for selective removal of a coproduct (i.e., acetone), leading to elimination of six undesirable reactions. Engineered orthogonality in substrate specificities of ω-TAs was exploited for kinetic control, enabling suppression of four additional reactions. Taken together, the net reaction pathway could be directed to two desired reactions (i.e., oxidative deamination of R-amine and reductive amination of the resulting ketone into antipode S-amine). This strategy afforded one-pot deracemization of various chiral amines with >99% eeS and 85-99% reaction yields of the resulting S-amine products. The in vitro cascade reaction could be successfully implemented in a live microbe using glucose or l-threonine as a cheap amino acceptor precursor, demonstrating a synthetic metabolic pathway enabling deracemization of chiral amines which has never been observed in living organisms.
| Original language | English |
|---|---|
| Pages (from-to) | 6945-6954 |
| Number of pages | 10 |
| Journal | ACS Catalysis |
| Volume | 9 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2019 Aug 2 |
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All Science Journal Classification (ASJC) codes
- Catalysis
- Chemistry(all)
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In Vitro and in Vivo One-Pot Deracemization of Chiral Amines by Reaction Pathway Control of Enantiocomplementary ω-Transaminases. / Han, Sang Woo; Jang, Youngho; Shin, Jong Shik.
In: ACS Catalysis, Vol. 9, No. 8, 02.08.2019, p. 6945-6954.Research output: Contribution to journal › Article
TY - JOUR
T1 - In Vitro and in Vivo One-Pot Deracemization of Chiral Amines by Reaction Pathway Control of Enantiocomplementary ω-Transaminases
AU - Han, Sang Woo
AU - Jang, Youngho
AU - Shin, Jong Shik
PY - 2019/8/2
Y1 - 2019/8/2
N2 - Biocatalytic cascade conversion of racemic amines into optically pure ones using enantiocomplementary ω-transaminases (ω-TAs) has been developed by thermodynamic and kinetic control of reaction pathways where 12 competing reactions occur with pyruvate and isopropylamine used as cosubstrates. Thermodynamic control was achieved under reduced pressure for selective removal of a coproduct (i.e., acetone), leading to elimination of six undesirable reactions. Engineered orthogonality in substrate specificities of ω-TAs was exploited for kinetic control, enabling suppression of four additional reactions. Taken together, the net reaction pathway could be directed to two desired reactions (i.e., oxidative deamination of R-amine and reductive amination of the resulting ketone into antipode S-amine). This strategy afforded one-pot deracemization of various chiral amines with >99% eeS and 85-99% reaction yields of the resulting S-amine products. The in vitro cascade reaction could be successfully implemented in a live microbe using glucose or l-threonine as a cheap amino acceptor precursor, demonstrating a synthetic metabolic pathway enabling deracemization of chiral amines which has never been observed in living organisms.
AB - Biocatalytic cascade conversion of racemic amines into optically pure ones using enantiocomplementary ω-transaminases (ω-TAs) has been developed by thermodynamic and kinetic control of reaction pathways where 12 competing reactions occur with pyruvate and isopropylamine used as cosubstrates. Thermodynamic control was achieved under reduced pressure for selective removal of a coproduct (i.e., acetone), leading to elimination of six undesirable reactions. Engineered orthogonality in substrate specificities of ω-TAs was exploited for kinetic control, enabling suppression of four additional reactions. Taken together, the net reaction pathway could be directed to two desired reactions (i.e., oxidative deamination of R-amine and reductive amination of the resulting ketone into antipode S-amine). This strategy afforded one-pot deracemization of various chiral amines with >99% eeS and 85-99% reaction yields of the resulting S-amine products. The in vitro cascade reaction could be successfully implemented in a live microbe using glucose or l-threonine as a cheap amino acceptor precursor, demonstrating a synthetic metabolic pathway enabling deracemization of chiral amines which has never been observed in living organisms.
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U2 - 10.1021/acscatal.9b01546
DO - 10.1021/acscatal.9b01546
M3 - Article
AN - SCOPUS:85070861623
VL - 9
SP - 6945
EP - 6954
JO - ACS Catalysis
JF - ACS Catalysis
SN - 2155-5435
IS - 8
ER -