High-density Cultivation in the Production of Microbial Products

Ramalingam, Subramanian; Thirumal, V.; Chistoserdov, Andrei Y.; Bajpai, Rakesh; Bader, Johannes; Popović, Milan

doi:10.15255/cabeq.2018.1394

Cited by 22 publications

(12 citation statements)

References 92 publications

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“…In general, a cell concentration of more than those achieved in conventional cultivation has been considered as the high cell density. Most experiments have dry cell weights ranging from 20 to 40 g/L, and if they are higher than 100 g/L they are designated as having a high cell density concentration (modified from [7]). They are normally operated with the fed-batch mode.…”

Section: Introductionmentioning

confidence: 99%

High Cell Density Cultivation of Saccharomyces cerevisiae with Intensive Multiple Sequential Batches Together with a Novel Technique of Fed-Batch at Cell Level (FBC)

et al. 2020

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High cell density cultivation (HCDC) is developed for the production of microbial biomasses and their products. They must be produced from high concentrations of substrate, e.g., glucose or sucrose. In batch culture, a high concentration of those sugars >40–50% (w/v) cannot efficiently be utilized because of a dissolved O2 limitation causing the Crabtree effect that produces toxic by-products, i.e., ethanol and/or acetate, that inhibit cell growth. To prevent this effect, the HCDC is conducted with the fed-batch strategies. However, it has many disadvantages, i.e., complicated operations. To overcome those problems, this study was designed to use a new, efficient C-source (carbon source) substrate, namely dextrin, an oligomer of glucose. It can be utilized by yeast at a very high concentration of ~100 g/L although using just batch cultivation. As it is gradually hydrolyzed to release glucose molecules and gradually assimilated into the cells as “fed-batch at the cell level” (FBC), it prevents the yeast cell system from undergoing the Crabtree effect. In this research, the types of medium, the types of sugar compared with dextrin, and the concentrations of yeast extract (YE) were studied. The batch production medium (BPM) with dextrin and YE performed very good results. The concentrations of dextrin for yeast cultivation were studied in the aerobic batch 5-L bioreactors. Its optimum concentration was at 90 g/L with 9 g/L of YE in 3× BPM. It was operated at 3 W/kg energy dissipation rate per unit mass (ε¯T) and 3 vvm airflow rate. Further, the intensive multiple sequential batch (IMSB) technique of high intensities of agitation speed and airflow was developed to achieve higher yield and productivity. The maximum values of cell biomass, specific growth rate, yield coefficient, productivity, and efficiency were at 55.17 g/L, 0.21 h−1, 0.54 g/g, 2.30 g/L/h, and 98.18%, respectively. The studies of cell growth kinetics, biochemical engineering mass balances, and fluid dynamics for the design of impeller speeds of the 5-L bioreactors during the cultivations of yeast using dextrin at the high concentrations were successful. The results can be used for the scale-up of bioreactor for the industrial production of yeast cell biomass at high concentrations.

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Section: Introductionmentioning

confidence: 99%

High Cell Density Cultivation of Saccharomyces cerevisiae with Intensive Multiple Sequential Batches Together with a Novel Technique of Fed-Batch at Cell Level (FBC)

et al. 2020

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“…Despite these advantages, certain technical barriers, such as inconsistent survival and stability during cultivation and variable microbial activity, have hindered the efficient application of microorganisms in fermentation. The stable, high density microbial cultivation required for the production of compounds on an industrial scale cannot be achieved under natural culture conditions 8 .…”

Section: Introductionmentioning

confidence: 99%

Aspergillus oryzae spore germination is enhanced by non-thermal atmospheric pressure plasma

Veerana

Lim

Choi

et al. 2019

Sci Rep

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Poor and unstable culture growth following isolation presents a technical barrier to the efficient application of beneficial microorganisms in the food industry. Non-thermal atmospheric pressure plasma is an effective tool that could overcome this barrier. The objective of this study was to investigate the potential of plasma to enhance spore germination, the initial step in fungal colonization, using Aspergillus oryzae , a beneficial filamentous fungus used in the fermentation industry. Treating fungal spores in background solutions of phosphate buffered saline (PBS) and potato dextrose broth (PDB) with micro dielectric barrier discharge plasma using nitrogen gas for 2 and 5 min, respectively, significantly increased the germination percentage. Spore swelling, the first step in germination, was accelerated following plasma treatment, indicating that plasma may be involved in loosening the spore surface. Plasma treatment depolarized spore membranes, elevated intracellular Ca 2+ levels, and activated mpkA, a MAP kinase, and the transcription of several germination-associated genes. Our results suggest that plasma enhances fungal spore germination by stimulating spore swelling, depolarizing the cell membrane, and activating calcium and MAPK signaling.

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“…For high cell density cultivation, it is also important to choose an optimum method of reactor operation, since environmental conditions affect the growth and product formation. Among these conditions, nutrient and substrate concentrations are important to be kept in specific ranges to avoid overfeeding or underfeeding [ 114 ].…”

Section: Modes Of Fermentation Processmentioning

confidence: 99%

Fermentation Strategies for Production of Pharmaceutical Terpenoids in Engineered Yeast

2021

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Terpenoids, also known as isoprenoids, are a broad and diverse class of plant natural products with significant industrial and pharmaceutical importance. Many of these natural products have antitumor, anti-inflammatory, antibacterial, antiviral, and antimalarial effects, support transdermal absorption, prevent and treat cardiovascular diseases, and have hypoglycemic activities. Production of these compounds are generally carried out through extraction from their natural sources or chemical synthesis. However, these processes are generally unsustainable, produce low yield, and result in wasting of substantial resources, most of them limited. Microbial production of terpenoids provides a sustainable and environment-friendly alternative. In recent years, the yeast Saccharomyces cerevisiae has become a suitable cell factory for industrial terpenoid biosynthesis due to developments in omics studies (genomics, transcriptomics, metabolomics, proteomics), and mathematical modeling. Besides that, fermentation development has a significant importance on achieving high titer, yield, and productivity (TYP) of these compounds. Up to now, there have been many studies and reviews reporting metabolic strategies for terpene biosynthesis. However, fermentation strategies have not been yet comprehensively discussed in the literature. This review summarizes recent studies of recombinant production of pharmaceutically important terpenoids by engineered yeast, S. cerevisiae, with special focus on fermentation strategies to increase TYP in order to meet industrial demands to feed the pharmaceutical market. Factors affecting recombinant terpenoids production are reviewed (strain design and fermentation parameters) and types of fermentation process (batch, fed-batch, and continuous) are discussed.

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High-density Cultivation in the Production of Microbial Products

Cited by 22 publications

References 92 publications

High Cell Density Cultivation of Saccharomyces cerevisiae with Intensive Multiple Sequential Batches Together with a Novel Technique of Fed-Batch at Cell Level (FBC)

High Cell Density Cultivation of Saccharomyces cerevisiae with Intensive Multiple Sequential Batches Together with a Novel Technique of Fed-Batch at Cell Level (FBC)

Aspergillus oryzae spore germination is enhanced by non-thermal atmospheric pressure plasma

Fermentation Strategies for Production of Pharmaceutical Terpenoids in Engineered Yeast

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