The strategies to reduce cost and improve productivity in DHA production by Aurantiochytrium sp.: from biochemical to genetic respects

Xu, Xinglian; Huang, Chang-Yi; Xu, Zhe-Xian; Xu, Huixia; Zhao, Wang; Yu, Xinjun

doi:10.1007/s00253-020-10927-y

Cited by 34 publications

(12 citation statements)

References 96 publications

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“…Fortification of DHA in infant formulas can promote development of the brain, retina, and nervous system. In adult, DHA helps maintain brain functions and it has positive and protective effects against several diseases, including arthritis, atherosclerosis, depression, diabetes, myocardial infarction, thrombosis, and cardiovascular diseases (Innis, 2008;Xu et al, 2020;Chi et al, 2022). DHA is also nutritionally and physiologically essential in animals.…”

Section: Introductionmentioning

confidence: 99%

“…It can, for instance, reduce skeletal malformation in larval Trachinotus ovatus and enhances immune function in juvenile grouper (Zhang et al, 2019). DHA can also improve various economic features of aquatic, cattle, and poultry animals, e.g., growth, development, and fecundity (Xu et al, 2020). Presently, most DHA in the market is derived from marine fish, in the form of fish oil or fish flesh, and seafood.…”

Section: Introductionmentioning

confidence: 99%

“…However, the use of pure carbon source, e.g., refined sugar, is actually not economically viable since it is costly. In some cases, cost of sugar could be almost 80% of the total medium cost (Patel et al, 2020a), making DHA production through Aurantiochytrium cultivation more expensive than the traditional fish oil (Xu et al, 2020;Chi et al, 2022). To lower the production cost, there have been attempts to substitute refined sugar with sugars derived from lignocellulosic biomass, e.g., Jurusalem artichoke (Yu et al, 2016), birch wood chips (Patel et al, 2019), and sugarcane bagasse (Nguyen et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Docosahexaenoic acid (DHA) production by Aurantiochytrium limacinum using cassava pulp hydrolysate as an alternative low-cost carbon source

et al. 2022

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Cost of nutrients is one of the major contributors to the production cost of docosahexaenoic acid (DHA) by thraustochytrids, and this remains the main challenge for economical and sustainable production of DHA. In the present study, cassava pulp (CP) was investigated as an alternative low-cost carbon source for DHA production by Aurantiochytrium limacinum SR21. Cultivation conditions, i.e., salinity level, type of nitrogen source, and concentrations of glucose and nitrogen sources, as well as pH, were optimized for cell growth. CP was enzymatically hydrolyzed, and used as the base medium, supplemented with artificial seawater salts, for DHA production under fed-batch cultivation. A. limacinum grew well at 18 g/L of NaCl (equivalent to 50% salinity level), and initial glucose concentration of 64 g/L, initial yeast extract concentration of 5 g/L, and pH 7.5 were optimum for cell growth. Fed-batch cultivation, with dissolved oxygen (DO) controlled at 10%, using CP-based medium as the carbon source gave a final cell dry mass of 26.3 ± 2.0 g/L, with 15.5 ± 0.1 g/L of lipid. DHA content in the lipid was 37.4 ± 1.5%, equivalent to 5.8 ± 0.3 g/L, and DHA productivity was 960 mg/(L·d). Medium-based economic analysis showed that an economic yield (EY) of this process was 0.86, which was higher than the 0.81 obtained using glucose as the substrate, assuming the same process and conditions. Overall, the results reveal that CP is a highly feasible feedstock for DHA production by A. limacinum SR21.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Docosahexaenoic acid (DHA) production by Aurantiochytrium limacinum using cassava pulp hydrolysate as an alternative low-cost carbon source

et al. 2022

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“…Due to the limited fish stock available, alternative sustainable sources of DHA are needed, and thraustochytrids have been developed as commercial DHA-rich oils producers [ 10 , 11 , 12 ]. However, DHA from thraustochytrids is currently considered to be less competitive in low-cost markets [ 13 ]. On the other hand, some thraustochytrids produce other substances, such as squalene [ 10 , 14 ], carotenoids [ 15 ], extracellular enzymes [ 16 ], and extracellular polysaccharides [ 17 ], that potentially could be valuable biproducts.…”

Section: Introductionmentioning

confidence: 99%

Method Development Progress in Genetic Engineering of Thraustochytrids

Rau

Ertesvåg

2021

Marine Drugs

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Thraustochytrids are unicellular, heterotrophic marine eukaryotes. Some species are known to store surplus carbon as intracellular lipids, and these also contain the long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA). Most vertebrates are unable to synthesize sufficient amounts of DHA, and this fatty acid is essential for, e.g., marine fish, domesticated animals, and humans. Thraustochytrids may also produce other commercially valuable fatty acids and isoprenoids. Due to the great potential of thraustochytrids as producers of DHA and other lipid-related molecules, a need for more knowledge on this group of organisms is needed. This necessitates the ability to do genetic manipulation of the different strains. Thus far, this has been obtained for a few strains, while it has failed for other strains. Here, we systematically review the genetic transformation methods used for different thraustochytrid strains, with the aim of aiding studies on strains not yet successfully transformed. The designs of transformation cassettes are also described and compared. Moreover, the potential problems when trying to establish transformation protocols in new thraustochytrid species/strains are discussed, along with suggestions utilized in other organisms to overcome similar challenges. The approaches discussed in this review could be a starting point when designing protocols for other non-model organisms.

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“…During the last decade there have been many efforts to improve productivities and yields of DHA production and lipid accumulation with traditional bioprocess means [15][16][17][18][19][20][21]. That includes both optimization of medium composition and bioreactor conditions [22]. The highest productivities have been obtained using rich media with high concentrations of yeast extract and/or peptones.…”

Section: Introductionmentioning

confidence: 99%

Combined Metabolome and Lipidome Analyses for In-Depth Characterization of Lipid Accumulation in the DHA Producing Aurantiochytrium sp. T66

et al. 2021

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Thraustochytrids are marine heterotrophic microorganisms known for their potential to accumulate docosahexaenoic acid (DHA)-enriched lipids. There have been many attempts to improve thraustochytrid DHA bioprocesses, especially through traditional optimization of cultivation and media conditions. Nevertheless, thraustochytrid-based bioprocesses are still not commercially competitive for high volume-low cost production of DHA. Thus, it is realized that genetic and metabolic engineering strategies are needed for the development of commercially competitive thraustochytrid DHA cell factories. Here, we present an analytical workflow for high resolution phenotyping at metabolite and lipid levels to generate deeper insight into the thraustochytrid physiology, with particular focus on central carbon and redox metabolism. We use time-series sampling during unlimited growth and nitrogen depleted triggering of DHA synthesis and lipid accumulation (LA) to show-case our methodology. The mass spectrometric absolute quantitative metabolite profiling covered glycolytic, pentose phosphate pathway (PPP) and tricarboxylic acid cycle (TCA) metabolites, amino acids, complete (deoxy)nucleoside phosphate pools, CoA and NAD metabolites, while semiquantitative high-resolution supercritical fluid chromatography MS/MS was applied for the lipid profiling. Interestingly, trace amounts of a triacylglycerols (TG) with DHA incorporated in all three acyl positions was detected, while TGs 16:0_16:0_22:6 and 16:0_22:6_22:6 were among the dominant lipid species. The metabolite profiling data indicated that lipid accumulation is not limited by availability of the acyl chain carbon precursor acetyl-CoA nor reducing power (NADPH) but rather points to the TG head group precursor glycerol-3-phosphate as the potential cause at the metabolite level for the gradual decline in lipid production throughout the cultivation. This high-resolution phenotyping provides new knowledge of changes in the central metabolism during growth and LA in thraustochytrids and will guide target selection for metabolic engineering needed for further improvements of this DHA cell factory.

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The strategies to reduce cost and improve productivity in DHA production by Aurantiochytrium sp.: from biochemical to genetic respects

Cited by 34 publications

References 96 publications

Docosahexaenoic acid (DHA) production by Aurantiochytrium limacinum using cassava pulp hydrolysate as an alternative low-cost carbon source

Docosahexaenoic acid (DHA) production by Aurantiochytrium limacinum using cassava pulp hydrolysate as an alternative low-cost carbon source

Method Development Progress in Genetic Engineering of Thraustochytrids

Combined Metabolome and Lipidome Analyses for In-Depth Characterization of Lipid Accumulation in the DHA Producing Aurantiochytrium sp. T66

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