Repeated fed-batch fermentation using biosensor online control for citric acid production by Yarrowia lipolytica

Moeller, Lucie; Grünberg, Mario; Zehnsdorf, Andreas; Aurich, Andreas; Bley, Thomas; Strehlitz, Beate

doi:10.1016/j.jbiotec.2011.03.013

Cited by 35 publications

(22 citation statements)

References 21 publications

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“…However, no trustworthy evidence is currently available on the history of commercial production, nor on the annual production volumes of citric acid derived from Y. lipolytica. The high potential of Y. lipolytica for organic acid production has been confirmed in the recent scientific literature not only for citric acid (Liu et al, 2013;Moeller et al, 2011;Rywinska et al, 2012), but also for isocitric, a-ketoglutaric, pyruvic, succinic and acetic acid (Chatzifragkou et al, 2011;Heretsch et al, 2008;Holz et al, 2011;Kamzolova et al, 2009Kamzolova et al, , 2012Otto et al, 2011Otto et al, , 2012 Yarrowia lipolytica has been chosen as production host for mannitol and erythritol (De Zeeuw & Tynan, 1973a, b;Tomaszewska et al, 2012). Since 2003, Baolingbao Biology Co., Ltd., from Shandong, China, produces erythritol with Y. lipolytica, for addition to foods as a nutritive sweetener, flavor enhancer, formulation aid, humectant, stabilizer and thickener, sequestrant and texturizer.…”

Section: Industrial Uses Of Y Lipolytica: Past Present and Futurementioning

confidence: 69%

Yarrowia lipolytica: Safety assessment of an oleaginous yeast with a great industrial potential

Groenewald

Boekhout

Neuvéglise

et al. 2013

Critical Reviews in Microbiology

397

288

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Yarrowia lipolytica has been developed as a production host for a large variety of biotechnological applications. Efficacy and safety studies have demonstrated the safe use of Yarrowia-derived products containing significant proportions of Yarrowia biomass (as for DuPont's eicosapentaenoic acid-rich oil) or with the yeast itself as the final product (as for British Petroleum's single-cell protein product). The natural occurrence of the species in food, particularly cheese, other dairy products and meat, is a further argument supporting its safety. The species causes rare opportunistic infections in severely immunocompromised or otherwise seriously ill people with other underlying diseases or conditions. The infections can be treated effectively by the use of regular antifungal drugs, and in some cases even disappeared spontaneously. Based on our assessment, we conclude that Y. lipolytica is a ''safe-to-use'' organism.

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Section: Industrial Uses Of Y Lipolytica: Past Present and Futurementioning

confidence: 69%

Yarrowia lipolytica: Safety assessment of an oleaginous yeast with a great industrial potential

Groenewald

Boekhout

Neuvéglise

et al. 2013

Critical Reviews in Microbiology

397

288

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“…The selectivity of the bioprocess for citric acid production of over 96% was obtained only in fermentations with genetically modified strains of Y. lipolytica . The comparison of the selectivity of the wild‐type strain Y. lipolytica H222 published in Moeller et al with those achieved after genetic modification of Y. lipolytica H222‐S4(p67ICL1)T5 shows a clear shift of the acid ratio in favor of citric acid (see Table ).…”

Section: Discussionmentioning

confidence: 93%

“…The determination of cell growth kinetics, selectivity, and productivities was carried out as described previously .…”

Section: Methodsmentioning

confidence: 99%

Citric acid production from sucrose by recombinant Yarrowia lipolytica using semicontinuous fermentation

Moeller

Zehnsdorf

Aurich

et al. 2012

Engineering in Life Sciences

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The genetically modified yeast strain Yarrowia lipolytica H222-S4(p67ICL1)T5 is able to utilize sucrose as a carbon source and to produce citric and isocitric acids in a more advantageous ratio as compared to its wild-type equivalent. In this study, the effect of pH of the fermentation broth (pH 6.0 and 7.0) and proteose-peptone addition on citric acid production by the recombinant yeast strain were investigated. It was found that the highest citric acid production occurred at pH 7.0 without any addition of proteose-peptone. Furthermore, two process strategies (fed-batch and repeated fed-batch) were tested for their applicability for use in citric acid production from sucrose by Y. lipolytica. Repeated fed-batch cultivation was found to be the most effective process strategy: in 3 days of cycle duration, approximately 80 g/L citric acid was produced, the yield was at least 0.57 g/g and the productivity was as much as 1.1 g/Lh. The selectivity of the bioprocess for citric acid was always higher than 90% from the very beginning of the fermentation due to the genetic modification, reaching values of up to 96.4% after 5 days of cycle duration.

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“…However, 50% medium replacement ratio was found to be the most suitable for the production of cellulase by Penicillium oxalicum RE-10 [15], and 50% medium replacement ratio was also used to achieve the best production of xylitol by Candida magnoliae TISTR 5663 [30]. One of the possible reasons for the difference in the optimal medium replacement ratio might be related to the types of microbes and products [15,31].…”

Section: Effects Of Medium Replacement Ratio On Dha Production In Repmentioning

confidence: 99%

Repeated fed-batch strategy and metabolomic analysis to achieve high docosahexaenoic acid productivity in Crypthecodinium cohnii

et al. 2020

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Background: Docosahexaenoic acid (DHA) is essential for human diet. However, high production cost of DHA using C. cohnii makes it currently less competitive commercially, which is mainly caused by low DHA productivity. In recent years, repeated fed-batch strategies have been evaluated for increasing the production of many fermentation products. The reduction in terms of stability of culture system was one of the major challenges for repeated fed-batch fermentation. However, the possible mechanisms responsible for the decreased stability of the culture system in the repeated fedbatch fermentation are so far less investigated, restricting the efforts to further improve the productivity. In this study, a repeated fed-batch strategy for DHA production using C. cohnii M-1-2 was evaluated to improve DHA productivity and reduce production cost, and then the underlying mechanisms related to the gradually decreased stability of the culture system in repeated fed-batch culture were explored through LC-and GC-MS metabolomic analyses. Results: It was discovered that glucose concentration at 15-27 g/L and 80% medium replacement ratio were suitable for the growth of C. cohnii M-1-2 during the repeated fed-batch culture. A four-cycle repeated fed-batch culture was successfully developed and assessed at the optimum cultivation parameters, resulting in increasing the total DHA productivity by 26.28% compared with the highest DHA productivity of 57.08 mg/L/h reported using C. cohnii, including the time required for preparing seed culture and fermentor. In addition, LC-and GC-MS metabolomics analyses showed that the gradually decreased nitrogen utilization capacity, and down-regulated glycolysis and TCA cycle were correlated with the decreased stability of the culture system during the long-time repeated fed-batch culture. At last, some biomarkers, such as Pyr, Cit, OXA, FUM, l-tryptophan, l-threonine, l-leucine, serotonin, and 4-guanidinobutyric acid, correlated with the stability of culture system of C. cohnii M-1-2 were identified. Conclusions: The study proved that repeated fed-batch cultivation was an efficient and energy-saving strategy for industrial production of DHA using C. cohnii, which could also be useful for cultivation of other microbes to improve productivity and reduce production cost. In addition, the mechanisms study at metabolite level can also be useful to further optimize production processes for C. cohnii and other microbes.

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Repeated fed-batch fermentation using biosensor online control for citric acid production by Yarrowia lipolytica

Cited by 35 publications

References 21 publications

Yarrowia lipolytica: Safety assessment of an oleaginous yeast with a great industrial potential

Yarrowia lipolytica: Safety assessment of an oleaginous yeast with a great industrial potential

Citric acid production from sucrose by recombinant Yarrowia lipolytica using semicontinuous fermentation

Repeated fed-batch strategy and metabolomic analysis to achieve high docosahexaenoic acid productivity in Crypthecodinium cohnii

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