Coevolution of the Activity and Thermostability of an ϵ‐Keto Ester Reductase for Better Synthesis of an (<i>R</i>)‐α‐Lipoic Acid Precursor

Xu, Yao; Chen, Qi; Zhang, Zhijun; Xu, Jian‐He; Zheng, Gao‐Wei

doi:10.1002/cbic.201900693

Cited by 15 publications

(10 citation statements)

References 38 publications

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“…Recently, the Xu and Zheng group reported the directed evolution of KREDs for the synthesis of several important chiral alcohols with high STY, including an Imbruvica precursor (25 g L −1 h −1 ), [31] an ( R )‐α‐lipoic acid precursor (24 g L −1 h −1 ), [32] and an Atorvastatin precursor 17 (44 g L −1 h −1 , Scheme 4). [30] For the production of 17 , a route initially developed by Codexis was followed [14] .…”

Section: Alcoholsmentioning

confidence: 99%

Biocatalysis: Enzymatic Synthesis for Industrial Applications

et al. 2020

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in 2007, followed by postdoctoral studies at York University (UK) and Greifswald University (Germany). In 2010, she transitionedto industry applying and developing biocatalytic technologies at Novacta in the UK, prior to joining Chemical Process Development at GSK, with responsibility for the development and implementation of new biocatalytic technologyi nboth pre-and post-commercialization routes. Since Dec. 2016, Radka is leading the Bioreactions group in GDC at the Novartis Institute for Biomedical Research in Basel, Switzerland. Jeffrey Moore obtained his PhD in Chemical Engineeringf rom the California Institute of Technology in 1996 as Frances Arnold's first Directed Evolution graduate student. His foundational work led to an evolved p-nitrobenzyl esterase and the Lonza Centenary Prize (1997). In 1996, he joined the Biocatalysis Group of Merck & Co.in Rahway NJ, spending two decades inventing new enzymes and new enzymatic processes. In 2018, he transitionedtothe Merck Protein EngineeringG roup responsible for evolving enzymes for the discovery,d evelopmenta nd commercials cale manufacture of medicines. He has been awarded aUS Presidential Green Chemistry Award (2010), the BioCat2012 Award (2012) and the Thomas Edison Inventorship Award (2014). Kai Baldenius studied chemistry in Hamburg and Southampton. He received his PhD for research in asymmetric organometallic catalysis, supervised by H. tom Dieck and H. B. Kagan. After his postdoc on natural product synthesis with K. C. Nicolaou at the Scripps Research Institute he joined BASF in 1993. Kai served BASF in various functions (R&D, production, marketing, sales) before he took the lead of BASF'sbiocatalysis research for almost ad efcade. He left BASF to become afree-lancing consultanti n2019 and in 2020 he has founded Baldenius Biotech Consulting. Uwe T. Bornscheuer studied chemistry and received his PhD in 1993 at Hannover University followed by apostdoc at Nagoya University (Japan). In 1998, he completed his Habilitation at Stuttgart University about the use of lipases and esterasesi n organic synthesis. He has been Professor at the Institute of Biochemistry at Greifswald University since 1999. Beside other awards, he received in 2008 the BioCat2008 Award. He was just recognized as "Chemistry Europe Fellow". His current research interest focuses on the discovery and engineering of enzymes from various classes for applications in organic synthesis, lipid modification, degradation of plastics or complex marine polysaccharides.

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Section: Alcoholsmentioning

confidence: 99%

Biocatalysis: Enzymatic Synthesis for Industrial Applications

et al. 2020

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“…( R )-α-Lipoic acid [ ( R )-14 ], for example, is a natural antioxidant, an enzyme cofactor and an over-the-counter nutritional supplement. Xu and Zheng and coworkers 62,63 used an ε-keto ester reductase (CpAR2) isolated from Candida parapsilosis for the enantioselective reduction of 8-chloro-6-oxooctanoate 11a , a key step in the synthesis of ( R )-14 (Scheme 6). Ethyl ( R )-8-chloro-6-hydroxy octanoate 11ba was obtained with a space-time yield of 530 g L −1 d −1 and >99% ee.…”

Section: Scope In the Enantioselective Synthesis Of Chiral Alcoholsmentioning

confidence: 99%

Engineering ketoreductases for the enantioselective synthesis of chiral alcohols

et al. 2023

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“…Although effective, the relative high loading of biocatalyst used (10 g/L) not only increases the production cost, but also makes the post‐reaction processing troublesome, such as foaming or formation of emulsions during the extraction of product from water with organic solvents. To address this issue, a directed evolution approach was adopted in order to increase the enzyme activity and thermal stability simultaneously [17] . By using epPCR, S131 and Q252 were identified as two hotpots influencing activity and stability, respectively.…”

Section: Creation Of One Stereocenter Through Kred‐catalyzed Reductionmentioning

confidence: 99%

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018–2020)

Yang

Liu

et al. 2021

The Chemical Record

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With the rapid development of genomic DNA sequencing, recombinant DNA expression, and protein engineering, biocatalysis has been increasingly and widely adopted in the synthesis of pharmaceuticals, bioactive molecules, fine chemicals, and agrochemicals. In this review, we have summarized the most recent advances achieved (2018–2020) in the research area of ketoreductase (KRED)‐catalyzed asymmetric synthesis of chiral secondary alcohol intermediates to pharmaceuticals and bioactive molecules. In the first part, synthesis of chiral alcohols with one stereocenter through the bioreduction of four different ketone classes, namely acyclic aliphatic ketones, benzyl or phenylethyl ketones, cyclic aliphatic ketones, and aryl ketones, is discussed. In the second part, KRED‐catalyzed dynamic reductive kinetic resolution and reductive desymmetrization are presented for the synthesis of chiral alcohols with two contiguous stereocenters.

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Coevolution of the Activity and Thermostability of an ϵ‐Keto Ester Reductase for Better Synthesis of an (R)‐α‐Lipoic Acid Precursor

Abstract: Figure 3. Scheme and results for the co-operative directed evolution of CpAR2's activity and thermostability.

Cited by 15 publications

References 38 publications

Biocatalysis: Enzymatic Synthesis for Industrial Applications

Biocatalysis: Enzymatic Synthesis for Industrial Applications

Engineering ketoreductases for the enantioselective synthesis of chiral alcohols

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018–2020)

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