Journal
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
Volume 9, Issue 11, Pages 4122-4129Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acssuschemeng.0c09075
Keywords
Biocatalysis; Amino transferase; Chiral amine; Enzyme engineering; Process development
Categories
Funding
- Biotechnology and Biological Sciences Research Council through the iCASE scheme
- Johnson Matthey [BB/M008770/1]
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The study investigates the synthesis of one of the smallest chiral amines, 2-aminobutane, using transaminases. Through screening a panel of transaminases, two candidates were identified and successfully immobilized to synthesize both enantiomers of 2-aminobutane with high enantioselectivity. The process demonstrated high atom economy and low E-factors for synthesizing (R)-2-aminobutane and (S)-2-aminobutane.
Chiral amines are a common feature of many active pharmaceutical ingredients. The synthesis of very small chiral amines is particularly challenging, even via biocatalytic routes, as the level of discrimination between similarly sized R-groups must be exceptional, yet their synthesis creates attractive building blocks that may then be used to prepare diverse compounds in further steps. Herein, the synthesis of one of the smallest chiral amines, 2-aminobutane, using transaminases, is being investigated. After screening a panel of mainly wild-type transaminases, two candidates were identified: an (S)-selective transaminase from Halomonas elongata (HEwT) and a precommercial (R)-selective transaminase from Johnson Matthey (*RTA-X43). Notably, a single strategic point mutation enhanced the enantioselectivity of HEwT from 45 to >99.5% ee. By covalently immobilizing these candidates, both enantiomers of 2-aminobutane were synthesized on a multigram scale, and the feasibility of isolation by distillation without the need for any solvents other than water was demonstrated. The atom economy of the process was calculated to be 56% and the E-factors (including waste generated during enzyme expression and immobilization) were 55 and 48 for the synthesis of (R)-2-aminobutane and (S)-2-aminobutane, respectively.
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