Fed-batch strategies for the enhanced biotransformation of cis-epoxysuccinate to L-(+)-tartrate

Abstract

L-(+)-Tartaric acid is a valuable organic acid with broad applications in the food, pharmaceutical, and chemical industries. Its eco-friendly synthesis typically relies on the enzymatic hydrolysis of cis-epoxysuccinate (CES) catalyzed by cis-epoxysuccinate hydrolases (CESHs), but conventional single-batch processes suffer from low space–time yields and poor continuity. To address these challenges, we devised two complementary fed-batch strategies to simplify the enzyme–product separation by exploiting differences in their solubilities. Strategy A employs carrier-free cross-linking immobilization of whole cells using 0.02% glutaraldehyde and 0.1% polyethylenimine. In this system, both the substrate sodium cis-epoxysuccinate (CESNa) and the product sodium L-(+)-tartrate remain soluble, while the enzyme is retained in the insoluble cell matrix. Under fed-batch operation, this configuration achieves a space–time yield of 150 g L⁻¹ h⁻¹. Strategy B uses cell-free extract of CESH to hydrolyze calcium cis-epoxysuccinate (CESCa) with inherently low solubility. Here, the enzyme is fully soluble but the L-(+)-tartrate formed precipitates as an insoluble calcium salt, allowing easy separation of the product from the reaction mixture. This approach overcomes potential substrate inhibition and minimizes sodium-ion discharge, delivering a space–time yield of 136 g L⁻¹ h⁻¹ and a specific productivity of 484 g_product/g_catalyst. Both the soluble-product/insoluble-enzyme system (A) and the insoluble-product/soluble-enzyme system (B) represent effective strategies to streamline downstream processing and markedly enhance productivity. Together, they offer a viable route to scalable and cost-effective industrial production of L-(+)-tartaric acid.

Keywords

L-(+)-Tartaric acid / cis-Epoxysuccinate hydrolase / Fed-batch reaction / Cell immobilization / Space–time yield

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Funding

Ministry of Science and Technology of the People's Republic of China(2020YFA0907700)

RIGHTS & PERMISSIONS

The Author(s)