Identification and metabolomic analysis of chemical modulators for lipid accumulation in Crypthecodinium cohnii

Li, Jinghan; Niu, Xiangfeng; Pei, Guangsheng; Xiao, Shan; Xiao-qing, Zhang; Chen, Lei; Zhang, Weiwen

doi:10.1016/j.biortech.2015.03.068

Cited by 50 publications

(28 citation statements)

References 33 publications

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“…LC-MS metabolomic analysis aiming mainly at unstable metabolites of central carbohydrate and energy metabolism [20] have been well established to probe the physiological change of C. cohnii M-1-2 [20,21]. Cell samples collected at 60 and 96 h of each cycle, which were both in the linear growth phases, were subjected to LC-MS based metabolic analysis to explore possible mechanisms related to the changes about the stability of culture system during repeated fed-batch culture of C. cohnii M-1-2.…”

Section: Lc-ms Based Metabolomic Analysis Of the Repeated Fed-batch Cmentioning

confidence: 99%

“…Metabolomic analysis is able to provide a metabolitelevel representation of the phenotype for organisms due to its capability to detect a large array of small molecule metabolites qualitatively and quantitatively [18,19]. In recent years, both liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS) based metabolomics have been widely applied to explore biology of various microalgae, including C. cohnii [20][21][22]. For example, the lipid accumulation mechanisms of C. cohnii responded to chemical modulators were explored using LC-MS based metabolomic analysis [21]; the glucose tolerance mechanisms of C. cohnii mutants obtained by adaptive laboratory evolution were analyzed by using GC-MS metabolomic analysis [22]; and the mechanisms of antioxidant on elevating lipid accumulation in C. cohnii were analyzed using integrated LC-and GC-MS metabolomic analyses [20].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Lc-ms Based Metabolomic Analysis Of the Repeated Fed-batch Cmentioning

confidence: 99%

Section: Introductionmentioning

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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“…Cells were harvested by centrifugation at 8000 × g for 8 min at 25°C (Eppendorf 5430R, Hamburg, Germany). Metabolite extraction and LC-MS analysis were performed according to a previously published protocol ( Li et al, 2015 ). Metabolomic data were normalized by interior control and cell number, and then submitted to principal component analysis (PCA) using SIMCA-P 11.5.…”

Section: Methodsmentioning

confidence: 99%

“…Crypthecodinium cohnii cells were cultivated in basal medium with 21 g/L glucose, harvested at 84 h by centrifugation (3500 × g ) (Eppendorf 5430R, Hamburg, Germany), and freeze-dried to generate a lyophilized algal powder. Lipid extraction and analysis were conducted based on the method described by Li et al (2015) .…”

Section: Methodsmentioning

confidence: 99%

“…For example, optimization of the fermentation parameters in fed-bath experiments led to a production of 109 g/L dry biomass, 61 g/L lipid, and a 19 g/L DHA in C. cohnii ( de Swaaf et al, 1999 , 2003 ; De Swaaf et al, 2003 ; Sijtsma and de Swaaf, 2004 ). In addition, chemical triggers such as butylated hydroxyanisol (BHA) ( Sui et al, 2014 ) and ethanolamine ( Li et al, 2015 ) were applied to directly stimulate lipid accumulation in C. cohnii . However, no study thus far has reported on using genetic engineering on DHA-producing C. cohnii .…”

Section: Introductionmentioning

confidence: 99%

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Genetic Engineering of Crypthecodinium cohnii to Increase Growth and Lipid Accumulation

et al. 2018

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In this study, we evaluated suitable selected markers and optimized transformation protocols to develop a new genetic transformation methodology for DHA-producing Crypthecodinium cohnii. Additionally, ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), potentially involved in CO2 fixation under autotrophic conditions, was selected as the target for construction of a gene knockdown mutant. Our results show that the constructs were successfully inserted into the C. cohnii chromosome by homologous recombination. Comparative analysis showed that deletion of the RuBisCO gene promoted cell growth and increased the lipid content of C. cohnii under heterotrophic conditions compared with those of the wild-type. The liquid chromatography-mass spectrometry (LC-MS) based metabolomic analysis showed that the metabolites involved in energy metabolism were upregulated, suggesting that the deletion of the RuBisCO gene may contribute to the re-direction of more carbon or energy toward growth and lipid accumulation under heterotrophic conditions.

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Exploitation of Fungal Endophytes as Bio‐Factories for Production of Functional Metabolites through Metabolic Engineering; Emphasizing on Taxol Production

Garyali

Tandon

Reddy

et al. 2019

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Identification and metabolomic analysis of chemical modulators for lipid accumulation in Crypthecodinium cohnii

Cited by 50 publications

References 33 publications

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

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

Genetic Engineering of Crypthecodinium cohnii to Increase Growth and Lipid Accumulation

Exploitation of Fungal Endophytes as Bio‐Factories for Production of Functional Metabolites through Metabolic Engineering; Emphasizing on Taxol Production

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