Development of Metabolically Engineered Saccharomyces cerevisiae Cells for the Production of Lactic Acid

Abstract

Interesting challenges from metabolically engineered Saccharomyces cerevisiae cells arise from the opportunity to obtain yeast strains useful for the production of chemical(s). In this paper, we describe the accumulation of lactic acid in the culture medium of growing, engineered yeast cells expressing a mammalian lactate dehydrogenase gene (LDH-A). High and reproducible productions (20 g/L) and productivities (up to 11 g/L/h) of lactic acid have been obtained by modulating the physiological growth conditions. Since yeast cells are acid tolerant and survive at very low pH values, the production of lactate can be avoided. In perspective, the approaches described could be useful for the production of lactic acid, outflanking the problems related to the synthesis from bacteria cells. In fact, during industrial productions, there is an inhibitory effect on the metabolic activities of the growing bacteria (i.e., Lactobacillus spp.) caused by the acid produced and by the low pH value. Thus, strategies to prevent the lowering of pH are conventional operations. These processes allow the production of lactate(s) and require the purification of the acid from its salt. The biotechnological implications of this study are also discussed.

Electrochemically Induced Crystallization as a Sustainable Method for Product Recovery of Building Block Chemicals: Techno-Economic Evaluation of Fumaric Acid Separation

“…Current biotechnological developments in the field of carboxylic acid production are focused on low pH fermentations. [31][32][33][34] Here, the acid is formed directly, obviating the need for a pH shift. This process will thus intrinsically exhibit a lower CO 2 footprint compared to state-of-the-art neutral fermentations.…”

The Current Status and Future Expectations in Industrial Production of Lactic Acid by Lactic Acid Bacteria

“…Exceptionally high levels of lactic acid (200 g/l) were produced in fed-batch fermentation. Yeasts have been metabolically engineered aiming at lactic acid production since 1990's [15]. A recent article reported on metabolic engineering of Candida utilis having pyruvate decarboxylase deleted and a bovine L-lactate dehydrogenase expressed under the pdc promoter resulting in the production of lactic acid with high yield from glucose (95 %) and reasonable RP (4.9 g/lh) ending up with lactic acid concentration of 103.3 g/l and more than 99.9 % enantiomeric purity [16].…”

The Effect of Pyruvate Decarboxylase Gene Knockout inSaccharomyces cerevisiaeonL-Lactic Acid Production

“…L-Lactic acid is generally produced using lactic acid bacteria, 2) whereas different approaches, such as genetically engineered yeasts, have been developed recently for large-scale production. Such metabolically engineered yeasts were first reported by Dequin and Barre 3) and Porro et al, 4) who showed that the recombinants yielded approximately 10 to 20 g of lactate/liter in the end. In both cases, a considerable amount of ethanol was produced concurrently because Saccharomyces cerevisiae predominantly produces ethanol under anaerobic conditions.…”