Engineering of an ene-reductase for producing the key intermediate of antiepileptic drug Brivaracetam.

Lili Sun, Yuan Liu, Hanxin Song, Jian Hao, Liang Lin

Abstract read

In one paragraph

Article in Applied microbiology and biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

2.0field-weighted citation impact, top 16% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Lili SunDepartment of Chemistry, Shanghai University, Shangda Road 99, Shanghai, China.

Yuan LiuSynthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education and College of Chemistry and Molecular Engineering, Peking University, Beijing, China.

Hanxin SongState Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Ling Ling Road 345, Shanghai, China.

Jian HaoDepartment of Chemistry, Shanghai University, Shangda Road 99, Shanghai, China.

Liang LinSynthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education and College of Chemistry and Molecular Engineering, Peking University, Beijing, China. lianglin@sioc.ac.cn.ORCID http://orcid.org/0000-0002-6705-1182

Peking University · CNShanghai University · CNChinese Academy of Sciences · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

(R)-4-Propyldihydrofuran-2(3H)-one (R-PDFO) is the key chiral intermediate for the antiepileptic drug Brivaracetam. Lacking a simple and economical method to approaching R-PDFO, the production of R-PDFO also remains environmentally unfriendly. Here, we developed a straightforward bioreduction way from easily synthesized 4-propylfuran-2(5H)-one (PFO) using ene-reductases. After screened with 27 ene-reductases, E116 stood out with 25.7% yield and 97% ee (R) as the starting enzyme. To improve the catalytic efficiency of E116, several rounds of directed evolution were first carried out. Through rational design, alanine scanning and random mutagenesis, engineered ene-reductase E116-M3 was obtained, with a 2.63-fold improvement in yields over WT, a 12.6-fold improvement in k

Indexed as

AnticonvulsantsOxidoreductasesMutagenesisPyrrolidinonesAnticonvulsantsbrivaracetamOxidoreductasesPyrrolidinonesBrivaracetamChiral intermediateEne-reductaseEnzyme engineering

Identifiers

PMID36710288

DOI10.1021/ol200394p

OpenAlexW4318454231

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.