Industrial Production of Lactic Acid

Miller, Carolyn; Fosmer, A.; Rush, Brian; McMullin, T.; Beacom, D.; Suominen, Pirkko

doi:10.1016/b978-0-12-809633-8.09142-1

Cited by 24 publications

(31 citation statements)

References 25 publications

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“…Moreover, manipulating the availability of intracellular redox by deleting the external NADH dehydrogenase genes has proven to be important to achieve high L-lactic acid production, resulting in a strain capable of producing 117 g/L of L-lactic acid in a fed-batch mode with pH controlled at 3.5 [14]. Cargill has developed a yeast-based process (undisclosed yeast species) for lactic acid production that was commercially implemented in 2008 [11]. Their yeast was engineered by deletion of pyruvate decarboxylase 1 gene and with integration of the L-lactate dehydrogenase gene from Lactobacillus (LDH, Figure 1).…”

Section: Lactic Acidmentioning

confidence: 99%

“…The main current application of lactic acid is however as a chemical intermediate for the production of polylactic acid, which is one of the most promising biodegradable polymers. The global annual production of lactic acid has been estimated at 370,000 tons in 2011, ranking among the high-volume products being biologically produced [11]. Biological production of lactic acid was traditionally carried out using lactic acid bacteria, but this process is not economical viable for large industrial-scale fermentations owing to the requirements of nutritionally rich media and moderate pH conditions [12].…”

Section: Lactic Acidmentioning

confidence: 99%

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Biobased organic acids production by metabolically engineered microorganisms

Chen

Nielsen

2016

Current Opinion in Biotechnology

143

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Section: Lactic Acidmentioning

confidence: 99%

Section: Lactic Acidmentioning

confidence: 99%

Biobased organic acids production by metabolically engineered microorganisms

Chen

Nielsen

2016

Current Opinion in Biotechnology

143

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“…Our setup enabled a continuous, real‐time, and noninvasive monitoring of main process parameters during bioproduction. As an initial proof‐of‐principle for more rapid screening within a few hours, the productivity of two engineered S. cerevisiae strains was evaluated on their ability to convert glucose into lactic acid under varying cultivation conditions (Miller et al, 2011; Sauer, Porro, Mattanovich, & Branduardi, 2010). The performances of the engineered strains were compared using our microfluidic bioreactor array‐on‐a‐chip platform (under various conditions) and standard shake flask cultivations to evaluate the efficacy of the miniaturized screening compared with benchmark tools (Figure 2a).…”

Section: Introductionmentioning

confidence: 99%

Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction

Totaro

Rothbauer

Steiger

et al. 2020

Biotech & Bioengineering

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A key challenge for bioprocess engineering is the identification of the optimum process conditions for the production of biochemical and biopharmaceutical compounds using prokaryotic as well as eukaryotic cell factories. Shake flasks and bench‐scale bioreactor systems are still the golden standard in the early stage of bioprocess development, though they are known to be expensive, time‐consuming, and labor‐intensive as well as lacking the throughput for efficient production optimizations. To bridge the technological gap between bioprocess optimization and upscaling, we have developed a microfluidic bioreactor array to reduce time and costs, and to increase throughput compared with traditional lab‐scale culture strategies. We present a multifunctional microfluidic device containing 12 individual bioreactors (Vt = 15 µl) in a 26 mm × 76 mm area with in‐line biosensing of dissolved oxygen and biomass concentration. Following initial device characterization, the bioreactor lab‐on‐a‐chip was used in a proof‐of‐principle study to identify the most productive cell line for lactic acid production out of two engineered yeast strains, evaluating whether it could reduce the time needed for collecting meaningful data compared with shake flasks cultures. Results of the study showed significant difference in the strains' productivity within 3 hr of operation exhibiting a 4‐ to 6‐fold higher lactic acid production, thus pointing at the potential of microfluidic technology as effective screening tool for fast and parallelizable industrial bioprocess development.

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“…Lactic acid (LA) is a colorless, odorless monocarboxylic acid naturally produced by many organisms. This weak acid has low buffering power and is tasteless, and has thus found broad use as an excipient in the food, cosmetics, pharmaceutical and chemical industries [ 1 , 2 ]. LA is listed in the GRAS inventory, the L-isomer being preferred for food and pharmaceutical applications due to the prevalence of the L-LA found in mammals [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…With mounting environmental pressure for sustainable industry, demand for PLA biomaterial is increasing demand for LA, for which the market is expected to hit 1 million tons by 2020 [ 4 ]. Nevertheless, the selling price of PLA still has to be cut by at least 50% to compete with fossil fuel-based plastics [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

L-lactic acid production by Aspergillus brasiliensis overexpressing the heterologous ldha gene from Rhizopus oryzae

Liaud

Rosso

Fabre³

et al. 2015

Microb Cell Fact

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BackgroundLactic acid is the building block of poly-lactic acid (PLA), a biopolymer that could be set to replace petroleum-based plastics. To make lactic acid production cost-effective, the production process should be carried out at low pH, in low-nutrient media, and with a low-cost carbon source. Yeasts have been engineered to produce high levels of lactic acid at low pH from glucose but not from carbohydrate polymers (e.g. cellulose, hemicellulose, starch). Aspergilli are versatile microbial cell factories able to naturally produce large amounts of organic acids at low pH and to metabolize cheap abundant carbon sources such as plant biomass. However, they have never been used for lactic acid production.ResultsTo investigate the feasibility of lactic acid production with Aspergillus, the NAD-dependent lactate dehydrogenase (LDH) responsible for lactic acid production by Rhizopus oryzae was produced in Aspergillus brasiliensis BRFM103. Among transformants, the best lactic acid producer, A. brasiliensis BRFM1877, integrated 6 ldhA gene copies, and intracellular LDH activity was 9.2 × 10−2 U/mg. At a final pH of 1.6, lactic acid titer reached 13.1 g/L (conversion yield: 26%, w/w) at 138 h in glucose-ammonium medium. This extreme pH drop was subsequently prevented by switching nitrogen source from ammonium sulfate to Na-nitrate, leading to a final pH of 3 and a lactic acid titer of 17.7 g/L (conversion yield: 47%, w/w) at 90 h of culture. Final titer was further improved to 32.2 g/L of lactic acid (conversion yield: 44%, w/w) by adding 20 g/L glucose to the culture medium at 96 h. This strain was ultimately able to produce lactic acid from xylose, arabinose, starch and xylan.ConclusionWe obtained the first Aspergillus strains able to produce large amounts of lactic acid by inserting recombinant ldhA genes from R. oryzae into a wild-type A. brasiliensis strain. pH regulation failed to significantly increase lactic acid production, but switching nitrogen source and changing culture feed enabled a 1.8-fold increase in conversion yields. The strain produced lactic acid from plant biomass. Our findings make A. brasiliensis a strong contender microorganism for low-pH acid production from various complex substrates, especially hemicellulose.

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Industrial Production of Lactic Acid

Cited by 24 publications

References 25 publications

Biobased organic acids production by metabolically engineered microorganisms

Biobased organic acids production by metabolically engineered microorganisms

Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction

L-lactic acid production by Aspergillus brasiliensis overexpressing the heterologous ldha gene from Rhizopus oryzae

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