Recent progress in microbial production of d-aspartate

Abstract

d-Aspartate (d-Asp) is a bioactive compound involved in neuroendocrine regulation and reproductive function in animals, including humans, with tissue-protective effects reported in experimental models, and has potential applications as a raw material for pharmaceuticals and functional food ingredients. It is also used as a side-chain precursor for semisynthetic antibiotics. An established industrial process for d-Asp uses enzymatic conversion by immobilized microbial cells with chemically synthesized d,l-Asp as the starting material and is constrained by dependence on chemical feedstock synthesis. Sustainable alternatives have therefore attracted attention: whole-cell bioconversion of exogenously supplied l-Asp has been demonstrated, whereas de novo production from a renewable carbon source has not yet been reported. This mini-review briefly notes the physiological and industrial contexts that motivate microbial production, and then focuses on the functions, biosynthesis, metabolism, and transport of d-Asp in microorganisms. We further discuss the screening of high-d-Asp-producing microorganisms using a high-throughput colorimetric assay based on d-aspartate oxidase, together with the molecular and cultivation characteristics of the strains identified. These studies indicate that racemization mediated by aspartate racemase, precursor supply via l-asparaginase, competing metabolism associated with bifunctional aspartate aminotransferase, and pH control during cultivation influence extracellular d-Asp accumulation; the contribution of membrane transport remains unresolved. Finally, we highlight the identification of d-Asp exporters, metabolic engineering of production strains, and optimization of cultivation processes as key future priorities for establishing a sustainable and reproducible fermentation platform for d-Asp production.