Membrane transporters in the bioproduction of organic acids: state of the art and future perspectives for industrial applications

Abstract

Organic acids such as monocarboxylic acids, dicarboxylic acids or even more complex molecules such as sugar acids, have displayed great applicability in the industry as these compounds are used as platform chemicals for polymer, food, agricultural and pharmaceutical sectors. Chemical synthesis of these compounds from petroleum derivatives is currently their major source of production. However, increasing environmental concerns have prompted the production of organic acids by microorganisms. The current trend is the exploitation of industrial biowastes to sustain microbial cell growth and valorize biomass conversion into organic acids. One of the major bottlenecks for the efficient and cost-effective bioproduction is the export of organic acids through the microbial plasma membrane. Membrane transporter proteins are crucial elements for the optimization of substrate import and final product export. Several transporters have been expressed in organic acid-producing species, resulting in increased final product titers in the extracellular medium and higher productivity levels. In this review, the state of the art of plasma membrane transport of organic acids is presented, along with the implications for industrial biotechnology.

Engineering of Yarrowia lipolytica transporters for high-efficient production of biobased succinic acid from glucose

“…These results demonstrated that C4-dicarboxylic acid transporters from different species can enhance the extracellular secretion of SA in Y. lipolytica . Among these transporters, SpMae1 has been widely applied to improve the microbial production of malate, succinate and fumarate [ 30 , 31 , 33 ], thus it can be used in the subsequent modification to obtain the SA over-production strains.

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Expanding the Knowledge on the Skillful Yeast Cyberlindnera jadinii

“…The production of biocompounds in high yields requires the optimization of several processes, including membrane transport of solutes to improve the entrance of substrates in the cell, exchange of products within cell organelles, and the efflux of metabolites to the extracellular medium, increasing the cell’s tolerance to toxic final products, and decreasing downstream processing costs [ 109 ]. In C. jadinii , several plasma transporters were physiologically or genetically characterized ( Figure 3 ).…”

“…The expression of membrane transporters allied to metabolic engineering tools is crucial to develop new and more efficient strains to produce bio-based compounds. Thus, increased knowledge of transporter proteins will enable the development of improved cell factories [ 109 , 143 , 144 ].…”

The Plasma Membrane at the Cornerstone Between Flexibility and Adaptability: Implications for Saccharomyces cerevisiae as a Cell Factory

“…Therefore, a proper export of the products of interest is often indispensable for a profitable and efficient cell factory. Researchers have been focusing on maximizing the export of the compounds of interest by overexpressing specific membrane transporters, engineering transporters for improved efficiency or even introducing heterologous transporters in the cell factory ( Boyarskiy and Tullman-Ercek, 2015 ; Kell et al, 2015 ; Erian et al, 2020 ; Soares-Silva et al, 2020 ). For more detailed information on the engineering of membrane transporters for industrial biotechnology applications, the reader should look the works mentioned above.…”