Recent advances in producing food additive L-malate: Chassis, substrate, pathway, fermentation regulation and application

Abstract

In addition to being an important intermediate in the TCA cycle, L-malate is also widely used in the chemical and beverage industries. Due to the resulting high demand, numerous studies investigated chemical methods to synthesize L-malate from petrochemical resources, but such approaches are hampered by complex downstream processing and environmental pollution. Accordingly, there is an urgent need to develop microbial methods for environmentally-friendly and economical L-malate biosynthesis. The rapid progress and understanding of DNA manipulation, cell physiology, and cell metabolism can improve industrial L-malate biosynthesis by applying intelligent biochemical strategies and advanced synthetic biology tools. In this paper, we mainly focused on biotechnological approaches for enhancing L-malate synthesis, encompassing the microbial chassis, substrate utilization, synthesis pathway, fermentation regulation, and industrial application. This review emphasizes the application of novel metabolic engineering strategies and synthetic biology tools combined with a deep understanding of microbial physiology to improve industrial L-malate biosynthesis in the future.

FIGURE 1

Recent advances in producing L‐malate chassis, substrate, and pathway. The main advances were involved in microbial chassis, substrate utilization, synthesis pathway, fermentation regulation and industrial application.

FIGURE 2

Co‐substrate for L‐malate production. The main advances were involved in CO₂ co‐substrate, ATP co‐substrate, and cofactor co‐substrate for L‐malate production.

FIGURE 3

The metabolic pathway for L‐malate production. 1,3‐BPG; 3‐PG, 1,3‐diphosphoglycerate, 3‐phosphoglycerate; aceA, isocitrate lyase; aceB, malate synthase; ackA, acetate kinase gene; acnAB, aconitate hydratase; adhE, alcohol dehydrogenase gene; CIT, citrate; FUM, fumarate; fumB, fumarase; gltA, citrate synthase; ISO, isocitric acid; ldhA, lactate dehydrogenase gene; MAL, L‐malate; mdh, malate dehydrogenase; OAA, oxaloacetic acid; pflB, fFormic acid lyase gene; poxB, pyruvate oxidase gene; SCO, succinyl‐coA; sdhABCD, succinate dehydrogenase; SUC, succinate; sucABCD, succinyl‐CoA synthetase; α‐KG, α‐Ketoglutaric acid.