DERA in Flow: Synthesis of a Statin Side Chain Precursor in Continuous Flow Employing Deoxyribose-5-Phosphate Aldolase Immobilized in Alginate-Luffa Matrix

Bianca Grabner, Yekaterina Pokhilchuk, Heidrun Gruber-Wölfler*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Statins, cholesterol-lowering drugs used for the treatment of coronary artery disease (CAD), are among the top 10 prescribed drugs worldwide. However, the synthesis of their characteristic side chain containing two chiral hydroxyl groups can be challenging. The application of deoxyribose-5-phosphate aldolase (DERA) is currently one of the most promising routes for the synthesis of this side chain. Herein, we describe the development of a continuous flow process for the biosynthesis of a side chain precursor. Design of experiments (DoE) was used to optimize the reaction conditions (pH value and temperature) in batch. A pH of 7.5 and a temperature of 32.5 °C were identified to be the optimal process settings within the reaction space considered. Additionally, an immobilization method was developed using the alginate-luffa matrix (ALM), which is a fast, simple, and inexpensive method for enzyme immobilization. Furthermore, it is non-toxic, biodegradable, and from renewable resources. The final continuous process was operated stable for 4 h and can produce up to 4.5 g of product per day.
Original languageEnglish
Article number137
JournalCatalysts
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • Alginate-luffa matrix
  • Continuous flow synthesis
  • Design of experiments
  • Immobilized DERA
  • Optimization
  • Statin side chain

ASJC Scopus subject areas

  • Catalysis
  • Physical and Theoretical Chemistry

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