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Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system

BACKGROUND: Deracemization, the transformation of the racemate into a single stereoisomeric product in 100% theoretical yield, is an appealing but challenging option for the asymmetric synthesis of optically pure chiral compounds as important pharmaceutical intermediates. To enhance the synthesis of...

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Autores principales: Zu, Han, Gu, Jie, Zhang, Hui, Fan, Anwen, Nie, Yao, Xu, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282177/
https://www.ncbi.nlm.nih.gov/pubmed/32513165
http://dx.doi.org/10.1186/s12934-020-01384-3
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author Zu, Han
Gu, Jie
Zhang, Hui
Fan, Anwen
Nie, Yao
Xu, Yan
author_facet Zu, Han
Gu, Jie
Zhang, Hui
Fan, Anwen
Nie, Yao
Xu, Yan
author_sort Zu, Han
collection PubMed
description BACKGROUND: Deracemization, the transformation of the racemate into a single stereoisomeric product in 100% theoretical yield, is an appealing but challenging option for the asymmetric synthesis of optically pure chiral compounds as important pharmaceutical intermediates. To enhance the synthesis of (R)-1,3-butanediol from the corresponding low-cost racemate with minimal substrate waste, we designed a stereoinverting cascade deracemization route and constructed the cascade reaction for the total conversion of racemic 1,3-butanediol into its (R)-enantiomer. This cascade reaction consisted of the absolutely enantioselective oxidation of (S)-1,3-butanediol by Candida parapsilosis QC-76 and the subsequent asymmetric reduction of the intermediate 4-hydroxy-2-butanone to (R)-1,3-butanediol by Pichia kudriavzevii QC-1. RESULTS: The key reaction conditions including choice of cosubstrate, pH, temperature, and rotation speed were optimized systematically and determined as follows: adding acetone as the cosubstrate at pH 8.0, a temperature of 30 °C, and rotation speed of 250 rpm for the first oxidation process; in the next reduction process, the optimal conditions were: adding glucose as the cosubstrate at pH 8.0, a temperature of 35 °C, and rotation speed of 200 rpm. By investigating the feasibility of the step-by-step method with one-pot experiment as a natural extension for performing the oxidation–reduction cascade, the step-by-step approach exhibited high efficiency for this cascade process from racemate to (R)-1,3-butanediol. Under optimal conditions, 20 g/L of the racemate transformed into 16.67 g/L of (R)-1,3-butanediol with 99.5% enantiomeric excess by the oxidation–reduction cascade system in a 200-mL bioreactor. CONCLUSIONS: The step-by-step cascade reaction efficiently produced (R)-1,3-butanediol from the racemate by biosynthesis and shows promising application prospects.
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spelling pubmed-72821772020-06-10 Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system Zu, Han Gu, Jie Zhang, Hui Fan, Anwen Nie, Yao Xu, Yan Microb Cell Fact Research BACKGROUND: Deracemization, the transformation of the racemate into a single stereoisomeric product in 100% theoretical yield, is an appealing but challenging option for the asymmetric synthesis of optically pure chiral compounds as important pharmaceutical intermediates. To enhance the synthesis of (R)-1,3-butanediol from the corresponding low-cost racemate with minimal substrate waste, we designed a stereoinverting cascade deracemization route and constructed the cascade reaction for the total conversion of racemic 1,3-butanediol into its (R)-enantiomer. This cascade reaction consisted of the absolutely enantioselective oxidation of (S)-1,3-butanediol by Candida parapsilosis QC-76 and the subsequent asymmetric reduction of the intermediate 4-hydroxy-2-butanone to (R)-1,3-butanediol by Pichia kudriavzevii QC-1. RESULTS: The key reaction conditions including choice of cosubstrate, pH, temperature, and rotation speed were optimized systematically and determined as follows: adding acetone as the cosubstrate at pH 8.0, a temperature of 30 °C, and rotation speed of 250 rpm for the first oxidation process; in the next reduction process, the optimal conditions were: adding glucose as the cosubstrate at pH 8.0, a temperature of 35 °C, and rotation speed of 200 rpm. By investigating the feasibility of the step-by-step method with one-pot experiment as a natural extension for performing the oxidation–reduction cascade, the step-by-step approach exhibited high efficiency for this cascade process from racemate to (R)-1,3-butanediol. Under optimal conditions, 20 g/L of the racemate transformed into 16.67 g/L of (R)-1,3-butanediol with 99.5% enantiomeric excess by the oxidation–reduction cascade system in a 200-mL bioreactor. CONCLUSIONS: The step-by-step cascade reaction efficiently produced (R)-1,3-butanediol from the racemate by biosynthesis and shows promising application prospects. BioMed Central 2020-06-08 /pmc/articles/PMC7282177/ /pubmed/32513165 http://dx.doi.org/10.1186/s12934-020-01384-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zu, Han
Gu, Jie
Zhang, Hui
Fan, Anwen
Nie, Yao
Xu, Yan
Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
title Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
title_full Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
title_fullStr Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
title_full_unstemmed Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
title_short Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
title_sort highly enantioselective synthesis of (r)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282177/
https://www.ncbi.nlm.nih.gov/pubmed/32513165
http://dx.doi.org/10.1186/s12934-020-01384-3
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