Efficient 1-Hydroxy-2-Butanone Production from 1,2-Butanediol by Whole Cells of Engineered E. coli

Abstract

1-Hydroxy-2-butanone (HB) is a key intermediate for anti-tuberculosis pharmaceutical ethambutol. Commercially available HB is primarily obtained by the oxidation of 1,2-butanediol (1,2-BD) using chemical catalysts. In present study, seven enzymes including diol dehydrogenases, secondary alcohol dehydrogenases and glycerol dehydrogenase were chosen to evaluate their abilities in the conversion of 1,2-BD to HB. The results showed that (2R, 3R)- and (2S, 3S)-butanediol dehydrogenase (BDH) from Serratia sp. T241 could efficiently transform (R)- and (S)-1,2-BD into HB respectively. Furthermore, two biocatalysts co-expressing (2R, 3R)-/(2S, 3S)-BDH, NADH oxidase and hemoglobin protein in Escherichia coli were developed to convert 1,2-BD mixture into HB, and the transformation conditions were optimized. Maximum HB yield of 341.35 and 188.80 mM could be achieved from 440 mM (R)-1,2-BD and 360 mM (S)-1,2-BD by E. coli (pET-rrbdh-nox-vgb) and E. coli (pET-ssbdh-nox-vgb) under the optimized conditions. In addition, two biocatalysts showed the ability in chiral resolution of 1,2-BD isomers, and 135.68 mM (S)-1,2-BD and 112.43 mM (R)-1,2-BD with the purity of 100 % could be obtained from 300 and 200 mM 1,2-BD mixture by E. coli (pET-rrbdh-nox-vgb) and E. coli (pET-ssbdh-nox-vgb), respectively. These results provided potential application for HB production from 1,2-BD mixture and chiral resolution of (R)-1,2-BD and (S)-1,2-BD.

Simultaneous Quantification of Twelve Compounds from Bamboo/Wood Vinegar by Gas Chromatography-Mass Spectrometry

“…Ketones are an important class of multi-purpose products used for the production of high-value-added chemicals [15]. For example, 1-hydroxy-2-butanone (HB) is a key intermediate in the anti-tuberculosis drug ethambutol [16]. The phenolic compounds in bamboo vinegar are the main active ingredients that exert antibacterial and antioxidant effects [17].…”

Metabolic Engineering of Escherichia coli for De Novo Production of 1,2-Butanediol

“…1,2-BDO is an important C4 diol with low viscosity and low freezing point, and is widely used in the synthesis of polyester polyols, plasticizers, cosmetics, and pharmaceuticals (such as ethambutol, levetiracetam, and brivaracetam). , Current production of 1,2-BDO relies entirely on chemical routes, primarily involving the hydration of epoxybutane and epoxypropane derived from nonrenewable fossil resources. Recently, a new approach for the conversion of biomass-based feedstock to 1,2-BDO by catalytic hydrocracking of starches and sugars has been developed .…”