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<p>In recent years, industrial biocatalysis has significantly advanced, largely due to innovations in DNA sequencing, bioinformatics, and protein engineering. However, the challenge of implementing biocatalysis at an industrial scale while ensuring sustainability and cost-effectiveness remains a critical barrier. This study presents the development of a flash thermal racemization protocol for chemoenzymatic dynamic kinetic resolution (FTR-CE-DKR) of chiral amines, encompassing an investigation of substrate scope, catalyst screening, and optimization studies. The outcomes of this research facilitated the successful scale-up of an industrially relevant amide within a recycle-batch platform, achieving unprecedented scales of up to 100 grams and space-time yield (STY) values of up to 73.2 g L⁻¹ h⁻¹. Furthermore, the process exhibited very favorable sustainability metrics when benchmarked against previous reports, including atom economy, reaction mass efficiency, and process mass intensity. These findings represent a significant milestone in the biocatalytic production of optically active amines.</p>

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Scalable and sustainable synthesis of chiral amines by biocatalysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月12日

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  • Matthew J. Takle,
  • David M. Maurer,
  • Philipp Staehle,
  • Joachim Dickhaut,
  • Christian Holtze,
  • Klaus Hellgardt,
  • King Kuok Mimi Hii

摘要

In recent years, industrial biocatalysis has significantly advanced, largely due to innovations in DNA sequencing, bioinformatics, and protein engineering. However, the challenge of implementing biocatalysis at an industrial scale while ensuring sustainability and cost-effectiveness remains a critical barrier. This study presents the development of a flash thermal racemization protocol for chemoenzymatic dynamic kinetic resolution (FTR-CE-DKR) of chiral amines, encompassing an investigation of substrate scope, catalyst screening, and optimization studies. The outcomes of this research facilitated the successful scale-up of an industrially relevant amide within a recycle-batch platform, achieving unprecedented scales of up to 100 grams and space-time yield (STY) values of up to 73.2 g L⁻¹ h⁻¹. Furthermore, the process exhibited very favorable sustainability metrics when benchmarked against previous reports, including atom economy, reaction mass efficiency, and process mass intensity. These findings represent a significant milestone in the biocatalytic production of optically active amines.