Engineering the antioxidant activity of Candida glabrata by enhancing malate biosynthesis

Abstract

Microbial cell factories are widely used for the bioproduction of various chemicals and biofuels. During this process, microorganisms will encounter many different stresses that frequently induce oxidative stress, thereby compromising cell growth. Here, Candida glabrata was used as a model system to engineer its oxidative stress tolerance by introducing malate biosynthetic capability. To further improve oxidative stress tolerance, malate biosynthesis pathway was optimized by fine-tuning expression strengths of pyruvate carboxylase and malate dehydrogenase, leading to an enhanced oxidative stress tolerance. Then, the physiological mechanism under this phenomenon was explored, and the antioxidative defense system showed a good improvement in ROS content, intracellular ATP level, superoxide dismutase and catalase activity. Further, the malate-producing C. glabrata was used to analyze their tolerance to artemisinin, showing that C. glabrata tolerance to artemisinin was significantly enhanced by introducing the malate biosynthetic capability. This study presented herein opens a window for the development of efficient cell factories with high tolerance to environment stress, facilitating the biosynthesis of pharmaceutical chemicals.

Keywords

Metabolic engineering / Stress tolerance / Malate / Artemisinin / Candida glabrata

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Jiangnan University