Application of omics technology in the study of DHA production by Aurantiochytrium

Abstract

Abstract: Docosahexaenoic acid (DHA) is a type of n-3 polyunsaturated fatty acid that is essential for human nutrition. Currently, DHA oil is commonly produced using Aurantiochytrium, and omics technologies are widely used to investigate the mechanisms underlying high DHA production in Aurantiochytrium. This provides a foundation for genetic modification and fermentation process control. In this paper, the history and main research directions of DHA production by Aurantiochytrium were summarized, and the application of omics technology in Aurantiochytrium was reviewed. It explains the progress made in genomics, transcriptomics, proteomics, metabolomics, and multi-omics approaches to reveal the mechanisms underlying high DHA production in Aurantiochytrium. It also discusses the current research on mathematical models based on omics data to elucidate the mechanisms of high DHA production in Aurantiochytrium, and provides an outlook on future developments and applications.

Key words: Aurantiochytrium, genomics, transcriptomes, proteomics, metabolomics

CLC Number:

TS222+.3

References

[1]ZHANG T T, XU J, WANG Y M, et al.Health benefits of dietary marine DHAEPA-enriched glycerophospholipids[J].Progress in Lipid Research, 2019, 75(100997):1-24
[2]DIAO J, SONG X, GUO T, et al.Cellular engineering strategies toward sustainable omega-3 long chain polyunsaturated fatty acids production: State of the art and perspectives [J]. [J].Biotechnology Advances, 2020, :1-15
[3]MENDES A, REIS A, VASCONCELOS R, et al.Crypthecodinium cohnii with emphasis on DHA production: a review[J].Journal of Applied Phycology, 2008, 21(2):199-214
[4]XU X, HUANG C, XU Z, et al.The strategies to reduce cost and improve productivity in DHA production by Aurantiochytrium sp: from biochemical to genetic respects[J].Applied Microbiology and Biotechnology, 2020, 104(22):9433-47
[5]GUPTA A, BARROW C J, PURI M.Omega-3 biotechnology: Thraustochytrids as a novel source of omega-3 oils[J].Biotechnology advances, 2012, 30(6):1733-45
[6]CHI G, XU Y, CAO X, et al.Production of polyunsaturated fatty acids by Schizochytrium (Aurantiochytrium) sp[J].Biotechnology Advances, 2022, 55(107897):1-28
[7]BELSKY G M.Axenic Culture Studies of a New Marine Phycomycete Possessing an Unusual Type of Asexual Reproduction[J].American Journal of Botany, 1964, 51(1):72-8
[8]YOKOYAMA R, HONDA D.Taxonomic rearrangement of the genus Schizochytrium sensu lato based on morphology,chemotaxonomic characteristics,and 18S rRNA gene phylogeny (Thraustochytriaceae,Labyrinthulomycetes): emendation for Schizochytrium and erection of Aurantiochytrium and Oblongichytrium gennov.[J].Mycoscience, 2007, 48(4):199-211
[9]MORABITO C, BOURNAUD C, MAES C, et al.The lipid metabolism in thraustochytrids[J].Progress in Lipid Research, 2019, 76(101007):1-18
[10]ELLENBOGEN B B, AARONSON S, GOLDSTEIN S, et al.Polyunsaturated fatty acids of aquatic fungi: possible phylogenetic significance[J].Comparative Biochemistry and Physiology, 1969, 29(2):805-11
[11]BARCLAY W R.Process for the heterotrophic production of microbial products with high concentrations of omega-3 highly unsaturated fatty acids [M]. US.
[12]NAKAHARA T, YOKOCHI T, HIGASHIHARA T, et al.Production of docosahexaenoic and docosapentaenoic acids by Schizochytrium spisolated from Yap Islands[J].Journal of the American Oil Chemists' Society, 1996, 73(11):1421-6
[13]LI Z, LING X, ZHOU H, et al.Screening chemical modulators of benzoic acid derivatives to improve lipid accumulation in Schizochytrium limacinum SR21 with metabolomics analysis[J].Biotechnology for Biofuels, 2019, 12(209):1-11
[14]LIANG M H, JIANG J G.Advancing oleaginous microorganisms to produce lipid via metabolic engineering technology[J].Progress in Lipid Research, 2013, 52(4):395-408
[15]WANG Q, HAN W, JIN W, et al.Docosahexaenoic acid production by Schizochytrium sp: review and prospect[J].Food Biotechnology, 2021, 35(2):111-35
[16]CHANG M, ZHANG T, LI L, et al.Choreography of multiple omics reveals the mechanism of lipid turnover in Schizochytrium spS31[J].Algal Research, 2021, 54(102182):1-9
[17]卢恒谦, 陈海琴, 唐鑫.组学技术在产油微生物中的应用[J].生物工程学报, 2021, 37(3):846-59
[18]JI X, MO K, REN L, et al.Genome Sequence of SchizochytriumspCCTCC M209059,an Effective Producer of Docosahexaenoic Acid-Rich Lipids[J].Genome Announcements, 2015, 3(4):e00819-15
[19]LIU B, ERTESVAG H, AASEN I M, et al.Draft genome sequence of the docosahexaenoic acid producing thraustochytrid Aurantiochytrium sp. T66 [J].[J].Genomics Data, 2016, 8(2016):115-116
[20]HIROAKI I, RYO K, RYOTA S, et al.A Possible Trifunctional β-Carotene Synthase Gene Identified in the Draft Genome of Aurantiochytrium spStrain KH105[J].Genes, 2018, 9(200):1-14
[21]HU F, CLEVENGER A L, ZHENG P, et al.Low-temperature effects on docosahexaenoic acid biosynthesis in Schizochytrium spTIO01 and its proposed underlying mechanism[J].Biotechnology for Biofuels, 2020, 13(172):1-14
[22]LIANG L, ZHENG X, FAN W, et al.Genome and Transcriptome Analyses Provide Insight Into the Omega-3 Long-Chain Polyunsaturated Fatty Acids Biosynthesis of Schizochytrium limacinum SR21[J].Frontiers in Microbiology, 2020, 11(687):1-15
[23]ZHAO X, DAUENPEN M, QU C, et al.Genomic analysis of genes involved in the biosynthesis of very long chain polyunsaturated fatty acids in Thraustochytrium sp26185[J].Lipids, 2016, 51(9):1065-75
[24]ZHU X, LI S, LIU L, et al.Genome Sequencing and Analysis of Thraustochytriidae spSZU445 Provides Novel Insights into the Polyunsaturated Fatty Acid Biosynthesis Pathway[J].Mar Drugs, 2020, 18(2):1-18
[25]PRANESHA PRABHAKARAN, NACHON RAETHONG, YUSUF NAZIR, et al.Whole genome analysis and elucidation of docosahexaenoic acid (DHA) biosynthetic pathway in Aurantiochytrium spSW1[J].Gene, 2022, 846(146850):1-9
[26]SONG Z, STAJICH J E, XIE Y, et al.Comparative analysis reveals unexpected genome features of newly isolated Thraustochytrids strains: on ecological function and PUFAs biosynthesis[J].BMC genomics, 2018, 19(541):1-16
[27]WANG Z, LOU S, HU F, et al.Complete mitochondrial genome of a DHA-rich protist Schizochytrium spTIO1101[J].Mitochondrial DNA Part B, 2016, 1(1):126-7
[28]GANUZA E, YANG S, AMEZQUITA M, et al.Genomics,Biology and Phylogeny Aurantiochytrium acetophilum spnov. (Thraustrochytriaceae),Including First Evidence of Sexual Reproduction[J].Protist, 2019, 170(2):209-32
[29]SU X, ZHOU M, HU P, et al.Whole-genome sequencing of an acidophilic Rhodotorula sp. ZM1 and its phenol-degrading capability under acidic conditions [J]. [J].Chemosphere, 2019, 232:76-86
[30]REN L, HU X, ZHAO X, et al.Transcriptomic Analysis of the Regulation of Lipid Fraction Migration and Fatty Acid Biosynthesis in Schizochytrium sp[J].Scientific reports, 2017, 7(3562):1-10
[31]NAOKI NAGANO K S, YOUSUKE TAOKA, YUJI OKITA, DAISKE HONDA, MAKOTO ITO AND MASAHIRO HAYASHI.Detection of Genes Involved in Fatty Acid Elongation and Desaturation in Thraustochytrid Marine Eukaryotes [J]. [J].Journal of Oleo Science, 2011, 60(9):475-481
[32]METZ J G, ROESSLER P, FACCIOTTI D, et al.Production of polyunsaturated fatty acids by polyketide synthases in both prokaryotes and eukaryotes[J].Science, 2001, 293(5528):290-3
[33]艾连中, 侯成杰.乳酸菌基因组代谢网络模型的研究进展[J].食品科学技术学报, 2021, 39(03):1-10
[34]YE C, QIAO W, YU X, et al.Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production [J]. [J].BMC genomics, 2015, 16(799):1-11
[35]BAO Z, ZHU Y, ZHANG K, et al.New insights into phenotypic heterogeneity for the distinct lipid accumulation of Schizochytrium spH016[J].Biotechnology for biofuels and bioproducts, 2022, 15(33):1-15
[36]SUN X M, REN L J, BI Z Q, et al.Adaptive evolution of microalgae Schizochytrium sp. under high salinity stress to alleviate oxidative damage and improve lipid biosynthesis [J].[J].Bioresour Technol,, 2018, 267:438-444
[37]ZHANG H Q, ZHAO X Y, ZHAO C, et al.Effects of glycerol and glucose on docosahexaenoic acid synthesis in Aurantiochyrium limacinum SFD-1502 by transcriptome analysis [J]. [J].Preparative Biochemistry & Biotechnology, 2022, :1-12
[38]CHEN W, ZHOU P-P, ZHANG M, et al.Transcriptome analysis reveals that up-regulation of the fatty acid synthase gene promotes the accumulation of docosahexaenoic acid in Schizochytrium sp. S056 when glycerol is used [J]. [J].Algal Research, 2016,, 15:83-92
[39]YE H, HE Y, XIE Y, et al.Fed-batch fermentation of mixed carbon source significantly enhances the production of docosahexaenoic acid in Thraustochytriidae sp. PKU#Mn16 by differentially regulating fatty acids biosynthetic pathways [J]. [J].Bioresource Technology, 2020, 297(122402.):1-10
[40]WANG D S, YU X J, ZHU X Y, et al.Transcriptome Mechanism of Utilizing Corn Steep Liquor as the Sole Nitrogen Resource for Lipid and DHA Biosynthesis in Marine Oleaginous Protist Aurantiochytrium sp[J].Biomolecules, 2019, 9(11):1-15
[41]HOANG M H, NGUYEN C, PHAM H Q, et al.Transcriptome sequencing and comparative analysis of Schizochytrium mangrovei PQ6 at different cultivation times[J].Biotechnology Letters, 2016, 38(10):1781-9
[42]YUE X H, CHEN W C, WANG Z M, et al.Lipid Distribution Pattern and Transcriptomic Insights Revealed the Potential Mechanism of Docosahexaenoic Acid Traffics in Schizochytrium spA-2[J].Journal of Agricultural and Food Chemistry, 2019, 67(34):9683-93
[43]HEGGESET T M B, ERTESVAG H, LIU B, et al.Lipid and DHA-production in Aurantiochytrium sp- Responses to nitrogen starvation and oxygen limitation revealed by analyses of production kinetics and global transcriptomes[J].Scientific reports, 2019, 9(19470):1-13
[44]JIANG J Y, ZHU S, ZHANG Y, et al.Integration of lipidomic and transcriptomic profiles reveals novel genes and regulatory mechanisms of Schizochytrium spin response to salt stress[J].Bioresource Technology, 2019, 294(122231):1-9
[45]DU H, LIAO X, GAO Z, et al.Effects of methanol on biomass,and fatty acid and carotenoid biosynthesis in Schizochytrium limacinum B4D1[J].Applied and Environmental Microbiology, 2019, 85(19):D-O
[46]ZHANG K, LI H, CHEN W, et al.Regulation of the Docosapentaenoic AcidDocosahexaenoic Acid Ratio (DPADHA Ratio) in Schizochytrium limacinum B4D1[J].Applied biochemistry and biotechnology, 2017, 182(1):67-81
[47]MA Z, TAN Y, CUI G, et al.Transcriptome and gene expression analysis of DHA producer Aurantiochytrium under low temperature conditions[J].Scientific reports, 2015, 5(14446):1-13
[48]BI Z Q, REN L J, HU X C, et al.Transcriptome and gene expression analysis of docosahexaenoic acid producer Schizochytrium spunder different oxygen supply conditions[J].Biotechnology for Biofuels, 2018, 11(249):1-13
[49]ZHANG S, HE Y, SEN B, et al.Alleviation of reactive oxygen species enhances PUFA accumulation in Schizochytrium sp. through regulating genes involved in lipid metabolism [J]. [J].Metabolic Engineering Communications, 2018, 6:39-48
[50]王京, 米芳, 高慧杰.加权基因共表达网络分析方法及其应用[J].家畜生态学报, 2023, 44(03):92-6
[51]BODZON-KULAKOWSKA A, BIERCZYNSKA-KRZYSIK A, DYLAG T, et al.Methods for samples preparation in proteomic research[J].Journal of Chromatography B, 2007, 849(1-2):1-31
[52]LING X, GUO J, ZHENG C, et al.Simple, effective protein extraction method and proteomics analysis from polyunsaturated fatty acids-producing micro-organisms [J]. [J].Bioprocess and biosystems engineering, 2015, 38:2331-2341
[53]NG I-S, YE C, ZHANG Z, et al.Daptomycin antibiotic production processes in fed-batch fermentation by Streptomyces roseosporus NRRL11379 with precursor effect and medium optimization [J].[J]. Bioprocess and Biosystems Engineering, 2014, 37:415-423
[54]MA Z, TIAN M, TAN Y, et al.Response mechanism of the docosahexaenoic acid producer Aurantiochytrium under cold stress [J]. [J].Algal Research, 2017, 25:191-199
[55]SHENE C, GARC S M, VERGARA D, et al.Production of lipids and proteome variation in a Chilean Thraustochytrium striatum strain cultured under different growth conditions [J]. [J].Marine biotechnology, 2019, 21:99-110
[56]BARTOSOVA Z, ERTESVAG H, NYFLOT E L, et al.Combined Metabolome and Lipidome Analyses for In-Depth Characterization of Lipid Accumulation in the DHA Producing Aurantiochytrium spT66[J].Metabolites, 2021, 11(3):D-O
[57]MARIAM I, KAREYA M S, NESAMMA A A, et al.Delineating metabolomic changes in native isolate Aurantiochytrium for production of docosahexaenoic acid in presence of varying carbon substrates [J]. [J].Algal Research, 2021, 55(102285):1-11
[58]LI Z, MENG T, HANG W, et al.Regulation of glucose and glycerol for production of docosahexaenoic acid in Schizochytrium limacinum SR21 with metabolomics analysis [J]. [J].Algal Research, 2021, 58(102415):1-10
[59]LI J, REN L J, SUN G-N, et al.Comparative Metabolomics Analysis of Docosahexaenoic Acid Fermentation Processes by Schizochytrium spunder Different Oxygen Availability Conditions[J].OMICS: A Journal of Integrative Biology, 2013, 17(5):269-81
[60]YANG Q, LU T, YAN J, et al.Regulation of polyunsaturated fatty acids synthesis by enhancing carotenoid-mediated endogenous antioxidant capacity in Schizochytrium sp [J].[J].Algal Research, 2021, 55(102238):1-13
[61]LI J, ZHOU H, PAN X, et al.The role of fluconazole in the regulation of fatty acid and unsaponifiable matter biosynthesis in Schizochytrium spMYA 1381[J].BMC microbiology, 2019, 19(256):1-13
[62]MA W, WANG Y Z, NONG F T, et al.An emerging simple and effective approach to increase the productivity of thraustochytrids microbial lipids by regulating glycolysis process and triacylglycerols' decomposition[J].Biotechnology for Biofuels, 2021, 14(247):1-14
[63]LIU Z X, YOU S, TANG B P, et al.Inositol as a new enhancer for improving lipid production and accumulation in Schizochytrium spSR21[J].Environmental Science and Pollution Research, 2019, 26(35):35497-508
[64]YU X J, SUN J, ZHENG J Y, et al.Metabolomics analysis reveals 6-benzylaminopurine as a stimulator for improving lipid and DHA accumulation of Aurantiochytrium sp[J].Journal of chemical technology and biotechnology, 2016, 91(4):1199-207
[65]YU X-J, SUN J, SUN Y-Q, et al.Metabolomics analysis of phytohormone gibberellin improving lipid and DHA accumulation in Aurantiochytrium sp [J]. [J].Biochemical Engineering Journal, 2016, (112):258-268
[66]LING X, ZHOU H, YANG Q, et al.Functions of Enyolreductase (ER) Domains of PKS Cluster in Lipid Synthesis and Enhancement of PUFAs Accumulation in Schizochytrium limacinum SR21 Using Triclosan as a Regulator of ER[J].Microorganisms, 2020, 8(300):1-17
[67]SHI Y, CHEN Z, LI Y, et al.Function of ORFC of the polyketide synthase gene cluster on fatty acid accumulation in Schizochytrium limacinum SR21[J].Biotechnology for Biofuels, 2021, 14(163):1-14
[68]LI Z, CHEN X, LI J, et al.Functions of PKS Genes in Lipid Synthesis of Schizochytrium spby Gene Disruption and Metabolomics Analysis[J].Marine biotechnology, 2018, 20(6):792-802
[69]LI Z, MENG T, LING X, et al.Overexpression of Malonyl-CoA: ACP Transacylase in Schizochytrium spto Improve Polyunsaturated Fatty Acid Production[J].Journal of Agricultural and Food Chemistry, 2018, 66(21):5382-91