Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production

Ye, Chao; Qiao, Weihua; Yu, Xiaobin; Ji, Xiao‐Jun; Huang, He; Collier, Jackie L.; Liu, Li

doi:10.1186/s12864-015-2042-y

Cited by 43 publications

(49 citation statements)

References 50 publications

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“…As shown in Fig. 4, the supplementation of l-glycine, l-alanine, l-cysteine, l-serine, l-threonine, and l-aspartate improved TAG production through enhancing the supply of acetylCoA, similar to the results reported for Schizochytrium limacinum (Ye et al 2015a). The TAG production rate was increased by 23.3, 27.7, 27.8, 42.0, 55.5, and 55.5%, respectively.…”

Section: Prediction Of Metabolic Engineering Strategies For Improvingsupporting

confidence: 76%

Reconstruction of genome-scale metabolic model of Yarrowia lipolytica and its application in overproduction of triacylglycerol

Wei

Jian

Chen

et al. 2017

Bioresour. Bioprocess.

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Background: Yarrowia lipolytica is widely studied as a non-conventional model yeast owing to the high level of lipid accumulation. Therein, triacylglycerol (TAG) is a major component of liposome. In order to investigate the TAG biosynthesis mechanism at a systematic level, a novel genome-scale metabolic model of Y. lipolytica was reconstructed based on a previous model iYL619_PCP published by our lab and another model iYali4 published by Kerkhoven et al. Results:The novel model iYL_2.0 contains 645 genes, 1083 metabolites, and 1471 reactions, which was validated more effective on simulations of specific growth rate. The precision of 29 carbon sources utilities reached up to 96.6% when simulated by iYL_2.0. In minimal growth medium, 111 genes were identified as essential for cell growth, whereas 66 essential genes were identified in yeast extract medium, which were verified by database of essential genes, suggesting a better prediction ability of iYL_2.0 in comparison with other existing models. In addition, potential metabolic engineering targets of improving TAG production were predicted by three in silico methods developed in-house, and the effects of amino acids supplementation were investigated based on model iYL_2.0. Conclusions:The reconstructed model iYL_2.0 is a powerful platform for efficiently optimizing the metabolism of TAG and systematically understanding the physiological mechanism of Y. lipolytica. Keywords:

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Section: Prediction Of Metabolic Engineering Strategies For Improvingsupporting

confidence: 76%

Reconstruction of genome-scale metabolic model of Yarrowia lipolytica and its application in overproduction of triacylglycerol

Wei

Jian

Chen

et al. 2017

Bioresour. Bioprocess.

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“…S31 enhanced growth and DHA synthesis, whereas a high oxygen transfer rate enhanced metabolic activity and promoted substrate assimilation to produce acetyl-CoA and NADPH for lipid synthesis 45 , confirming an earlier report 40 . Based on the genome annotation results of S. limacinum SR21, Ye et al, (2015) suggested that this microorganism doesn't have delta-4 desaturase and some ORFs were considered to be as PKS proteins. These results confirm that the DHA could not be synthesized by FAS route but rather utilizes PKS pathway for DHA synthesis 46 .…”

Section: Optimization Of Aeration Rate and Glucose Concentration Durimentioning

confidence: 99%

Co-production of DHA and squalene by thraustochytrid from forest biomass

Patel

Liefeldt

Rova

et al. 2020

Sci Rep

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Omega-3 fatty acids, and specifically docosahexaenoic acid (DHA), are important and essential nutrients for human health. thraustochytrids are recognised as commercial strains for nutraceuticals production, they are group of marine oleaginous microorganisms capable of co-synthesis of DHA and other valuable carotenoids in their cellular compartment. the present study sought to optimize DHA and squalene production by the thraustochytrid Schizochytrium limacinum SR21. The highest biomass yield (0.46 g/g substrate) and lipid productivity (0.239 g/g substrate) were observed with 60 g/L of glucose, following cultivation in a bioreactor, with the DHA content to be 67.76% w/w total lipids. to reduce costs, cheaper feedstocks and simultaneous production of various value-added products for pharmaceutical or energy use should be attempted. To this end, we replaced pure glucose with organosolv-pretreated spruce hydrolysate and assessed the simultaneous production of DHA and squalene from S. limacinum SR21. After the 72 h of cultivation period in bioreactor, the maximum DHA content was observed to 66.72% w/w total lipids that was corresponded to 10.15 g/L of DHA concentration. While the highest DHA productivity was 3.38 ± 0.27 g/L/d and squalene reached a total of 933.72 ± 6.53 mg/L (16.34 ± 1.81 mg/ g CDW). In summary, we show that the co-production of DHA and squalene makes S. limacinum SR21 appropriate strain for commercial-scale production of nutraceuticals. Omega-6 (n-6) and omega-3 (n-3) are polyunsaturated fatty acids (PUFAs), whose precursors include linoleic acid and alpha-linolenic acid. They are considered essential because humans cannot synthesize them due to insufficient levels of elongases and delta-6-desaturases 1,2. Although conversion of alpha-linolenic acid into omega-3 fatty acids, such as eicosapentaenoic acid (C 20:5n−3), docosapentaenoic acid (C 22:5n−3), and docosahexaenoic acid (C 22:6n−3 , DHA) occurs in humans, it happens at a very slow rate 3 and so these fatty acids must be provided by the diet. These PUFAs have several health benefits and have been found to be very effective in the preventions and treatment of fetal diseases 4. DHA plays a major role in cell signalling and is found mainly in the brain and retina tissues 5. Additionally, it acts as an anti-inflammatory agent, a precursor of several metabolites and potent lipid mediators, and could be used to treat several cardiovascular or neurologic disorders, such as hypertension and Alzheimer's 6. Fish of the Salmonidae, Scombridae, and Clupeidae families have been the sole commercial source of DHA as their oil contains approximately 20 to 30% DHA 3. However, DHA purification and concentration from fish oil is costly and the resulting oil quality depends on species, location, and pollution 7. Furthermore, fish-derived DHA is unsuitable for vegetarians, and diminishing fish stocks together with marine pollution limit the increasing demand for DHA 7. Oils from genetically engineered plant oilseeds, such as Brassica juncea, Arabidopsis thaliana, an...

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“…The second half of the FAS pathway can be divided into two subpathways. One subpathway starts with C18:3 (9,12,15), the biosynthesis of which involves the delta-6 desaturation of C18:3 (9,12,15) to C18:4 (6,9,12,15), the elongation of C18:4 (6,9,12,15) to C20:4 (8,11,14,17), and the delta-5 desaturation of C20:4 (8,11,14,17) to C20:5 (5,8,11,14,17) followed by another elongation of C20:5 (5,8,11,14,17) to C22:5 (7,10,13,16,19) and a final delta-4 desaturation of C22:5 (7,10,13,16,19) to C22:6 (4,7,10,13,16,19). The same enzymes are involved in both the first and second pathways.…”

Section: Analysis Of Genes Involved In Long-chain Fatty Acid (Lcfa) Bmentioning

confidence: 99%

“…However, for the Thraustochytrids species, the available genomic information is limited. Ye et al reconstructed a genome-scale metabolic map of Schizochytrium limacinum SR21 and found that the biosynthesis of DHA via the PKS pathway requires abundant acetyl-CoA and NADPH, and that 30 genes were predicted as potential targets for DHA overproduction [19]. Comparative genomic analysis revealed that both the FAS and PKS pathways of PUFA production were incomplete and that secreted carbohydrate-active enzymes were remarkably consumed in the genomes of two newly isolated Thraustochytrids strains, Mn4 and SW8 [20].…”

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confidence: 99%

Genome Sequencing and Analysis of Thraustochytriidae sp. SZU445 Provides Novel Insights into the Polyunsaturated Fatty Acid Biosynthesis Pathway

Zhu

Liu

et al. 2020

Marine Drugs

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Thraustochytriidae sp. have broadly gained attention as a prospective resource for the production of omega-3 fatty acids production in significant quantities. In this study, the whole genome of Thraustochytriidae sp. SZU445, which produces high levels of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), was sequenced and subjected to protein annotation. The obtained clean reads (63.55 Mb in total) were assembled into 54 contigs and 25 scaffolds, with maximum and minimum lengths of 400 and 0.0054 Mb, respectively. A total of 3513 genes (24.84%) were identified, which could be classified into six pathways and 44 pathway groups, of which 68 genes (1.93%) were involved in lipid metabolism. In the Gene Ontology database, 22,436 genes were annotated as cellular component (8579 genes, 38.24%), molecular function (5236 genes, 23.34%), and biological process (8621 genes, 38.42%). Four enzymes corresponding to the classic fatty acid synthase (FAS) pathway and three enzymes corresponding to the classic polyketide synthase (PKS) pathway were identified in Thraustochytriidae sp. SZU445. Although PKS pathway-associated dehydratase and isomerase enzymes were not detected in Thraustochytriidae sp. SZU445, a putative DHA-and DPA-specific fatty acid pathway was identified.2 of 18 in a number of previous studies, and include the proper development of infant brain and eyes [1,2]; cardiovascular disease prevention [3]; antioxidative, anti-inflammatory [4] as well as anti-cancer properties [5], and the prevention of Alzheimer's disease [6]. Currently, ocean fish are the primary PUFA production source. However, because of the drawbacks of a fishy odor, the accumulation of contaminants, and declining fish stock, it is necessary to identify other sustainable and relatively safer alternative sources of PUFA [7].Thraustochytrids, a single-celled eukaryotic marine protist belonging to the class Labyrinthulomycetes, can accumulate large amounts of DHA, resulting in these organisms having attracted a great deal of scientific and industrial interest. Research has shown that some thraustochytrid strains can be cultivated to yield high biomasses containing substantial quantities of lipids abundant in PUFAs [8]. There is an abundance of research on the optimization of fermentation parameters in terms of salinity [9], pH, temperature [10], and cultivation medium [11] for high DHA production. Besides, metabolic engineering is also used as a promising approach to promote DHA productivity. Recent research has indicated that DHA is synthesized by two distinct pathways in thraustochytrid: the fatty acid synthase (FAS) pathway and the polyketide synthase (PKS) pathway [12]. The standard FAS pathway synthesizes fatty acids through a series of elongase-and desaturase-catalyzed reactions. Delta-4 desaturase, delta-5 desaturase, and delta-12 desaturase have been reported in Thraustochytrium aureum ATCC 34304 [13][14][15], and delta-5 elongase, delta-6 elongase, and delta-9 elongase have also been successfully identified in some thraustochytrid str...

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Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production

Cited by 43 publications

References 50 publications

Reconstruction of genome-scale metabolic model of Yarrowia lipolytica and its application in overproduction of triacylglycerol

Reconstruction of genome-scale metabolic model of Yarrowia lipolytica and its application in overproduction of triacylglycerol

Co-production of DHA and squalene by thraustochytrid from forest biomass

Genome Sequencing and Analysis of Thraustochytriidae sp. SZU445 Provides Novel Insights into the Polyunsaturated Fatty Acid Biosynthesis Pathway

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