Microbial cell factories for gamma-linolenic acid biosynthesis: metabolic engineering, downstream processing, and future perspectives
Jie Qiao , Wei Wang , Peiyao Duan , Zhili Zhang , Rongrong Yang , Haiyang Cui , Xiujuan Li
Bioresources and Bioprocessing ›› 2026, Vol. 13 ›› Issue (1) : 152
Gamma-linolenic acid (GLA) is a vital anti-inflammatory polyunsaturated fatty acid, yet its traditional supply from plant seeds such as evening primrose and borage is constrained by low yields and climatic instability. Consequently, microbial cell factories present a sustainable and season-independent alternative for scalable GLA production. This review critically synthesizes recent biotechnological advancements in utilizing oleaginous microorganisms as production platforms. It systematically elucidates the microbial lipid biosynthesis pathways and evaluates strategies to enhance GLA accumulation, with particular emphasis on rational metabolic engineering. Furthermore, emerging technologies for microbial lipid production, alongside the latest progress in industrial-scale applications, are thoroughly examined. Finally, comprehensive insights are provided to guide the optimization of the entire value chain, ranging from upstream strain engineering to downstream processing.
Gamma-linolenic acid (GLA) / Microbial lipids / Metabolic engineering / Biosynthesis / Machine learning
| [1] |
|
| [2] |
Ahamefule CS, Ogbonna CN, Ahamefule BC, Ogbonna I, Ogbonna J (2023) Chap. 7 - Lipids and fatty acids from microalgae. In Handbook of Food and Feed from Microalgae, Jacob-Lopes, E.; Queiroz, M. I.; Maroneze, M. M.; Zepka, L. Q., Eds. Academic Press: ; pp 73–86 |
| [3] |
|
| [4] |
|
| [5] |
|
| [6] |
|
| [7] |
|
| [8] |
|
| [9] |
|
| [10] |
|
| [11] |
|
| [12] |
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
|
| [20] |
|
| [21] |
|
| [22] |
|
| [23] |
|
| [24] |
|
| [25] |
|
| [26] |
|
| [27] |
|
| [28] |
|
| [29] |
|
| [30] |
|
| [31] |
Conti E, Stredansky M, Stredanska S, Zanetti F (2001) γ-Linolenic acid production by solid-state fermentation of Mucorales strains on cereals. Bioresour Technol 76(3):283–286 |
| [32] |
|
| [33] |
|
| [34] |
|
| [35] |
|
| [36] |
|
| [37] |
|
| [38] |
|
| [39] |
|
| [40] |
|
| [41] |
|
| [42] |
|
| [43] |
|
| [44] |
|
| [45] |
|
| [46] |
|
| [47] |
|
| [48] |
|
| [49] |
|
| [50] |
|
| [51] |
|
| [52] |
|
| [53] |
|
| [54] |
|
| [55] |
|
| [56] |
Gazem RAA, Chandrashekariah SA (2014) Omega fatty acids in health and disease: a review. J Pharm Res 8(8), 1027–1044 |
| [57] |
|
| [58] |
|
| [59] |
|
| [60] |
|
| [61] |
|
| [62] |
|
| [63] |
|
| [64] |
|
| [65] |
|
| [66] |
|
| [67] |
|
| [68] |
|
| [69] |
|
| [70] |
|
| [71] |
|
| [72] |
|
| [73] |
|
| [74] |
|
| [75] |
|
| [76] |
|
| [77] |
|
| [78] |
|
| [79] |
|
| [80] |
|
| [81] |
|
| [82] |
|
| [83] |
|
| [84] |
|
| [85] |
|
| [86] |
|
| [87] |
|
| [88] |
|
| [89] |
|
| [90] |
|
| [91] |
Kapoor R, Nair H (2020) Gamma Linolenic acid: sources and functions. In Bailey’s Ind. Oil Fat Prod., 1 ed.; Shahidi, F., Ed. Wiley: ; pp 1–45 |
| [92] |
|
| [93] |
|
| [94] |
|
| [95] |
|
| [96] |
|
| [97] |
|
| [98] |
|
| [99] |
|
| [100] |
|
| [101] |
|
| [102] |
|
| [103] |
|
| [104] |
|
| [105] |
|
| [106] |
|
| [107] |
|
| [108] |
|
| [109] |
|
| [110] |
|
| [111] |
|
| [112] |
|
| [113] |
|
| [114] |
|
| [115] |
|
| [116] |
|
| [117] |
|
| [118] |
Mantri BU, Vahidinasab M, Berensmeier S (2025) Engineering strategies for fungal cell disruption in biotechnological applications. Eng Life Sci 25 (12):e70061 |
| [119] |
|
| [120] |
Moreno Martínez P, Ortiz-Martínez VM, Sánchez Segado S, Salar-García MJ, los Ríos AP d.; Hernández Fernández FJ, Lozano-Blanco LJ, Godínez C (2022) Deep eutectic solvents for the extraction of fatty acids from microalgae biomass: recovery of omega-3 eicosapentaenoic acid. Sep. Purif. Technol. 300:121842 |
| [121] |
|
| [122] |
|
| [123] |
|
| [124] |
Michael R, Kaestel-Hansen J, Morch Groth P, Bartels S, Salomon J, Tian P, Hatzakis NS, Boomsma W (2024) A systematic analysis of regression models for protein engineering. PLoS Comput Biol 20 (5): e1012061 |
| [125] |
|
| [126] |
Mititelu M, Lupuliasa D, Neacsu SM, Olteanu G, Busnatu SS, Mihai A, Popovici V, Maru N, Boroghina SC, Mihai S, Ionita-Mindrican CB, Scafa-Udriste A (2024) Polyunsaturated fatty acids and human health: a key to modern nutritional balance in association with polyphenolic compounds from food sources. Foods 14 (1) :46-70 |
| [127] |
|
| [128] |
|
| [129] |
|
| [130] |
|
| [131] |
|
| [132] |
Mustonen AM, Nieminen P (2023) Dihomo-gamma-Linolenic acid (20:3n-6)-metabolism, derivatives, and potential significance in chronic inflammation. Int J Mol Sci 24 (3):2116 -2141 |
| [133] |
|
| [134] |
|
| [135] |
|
| [136] |
Ochsenreither K, Glück C, Stressler T, Fischer L, Syldatk C (2016) Production strategies and applications of microbial single cell oils. Front. Microbiol. 7:1539 |
| [137] |
|
| [138] |
|
| [139] |
|
| [140] |
|
| [141] |
|
| [142] |
|
| [143] |
|
| [144] |
|
| [145] |
Ratledge C (2005) Microbial production of gamma-Linolenic acid. In Handbook of Functional Lipids, ; pp 19–45 |
| [146] |
|
| [147] |
|
| [148] |
|
| [149] |
|
| [150] |
|
| [151] |
|
| [152] |
Rizzo G, Baroni L, Lombardo M (2023) Promising sources of plant-derived polyunsaturated fatty acids: a narrative review. Int J Environ Res Public Health 20(3):1683-1704 |
| [153] |
|
| [154] |
|
| [155] |
|
| [156] |
|
| [157] |
|
| [158] |
|
| [159] |
|
| [160] |
|
| [161] |
|
| [162] |
|
| [163] |
Shaw R (1966) The polyunsaturated fatty acids of microorganisms. In Adv. Lipid Res., Paoletti, R.; Kritchevsky, D., Eds. Elsevier: ; Vol. 4, pp 107–174 |
| [164] |
|
| [165] |
|
| [166] |
|
| [167] |
|
| [168] |
|
| [169] |
|
| [170] |
Song Z, Rogers A, Cho BA, Jing K, Zhang D (2022) Kinetic modelling of γ-linolenic acid production by Cunninghamella echinulata. In Comput. Aided Chem. Eng., Montastruc, L.; Negny, S., Eds. Elsevier: ; Vol. 51, pp 109–114 |
| [171] |
|
| [172] |
|
| [173] |
|
| [174] |
|
| [175] |
|
| [176] |
|
| [177] |
|
| [178] |
|
| [179] |
|
| [180] |
|
| [181] |
Tang X, Chen H, Chen YQ, Chen W, Garre V, Song Y, Ratledge C (2015) Comparison of biochemical activities between high and low lipid-producing strains of Mucor circinelloides: an explanation for the high oleaginicity of strain WJ11. PLoS ONE 10 (6): e0128396 |
| [182] |
Tanwar B, Goyal A, Kumar V, Rasane P, Sihag MK (2021) Borage (Borago officinalis) Seed. In: Tanwar B, Goyal A (eds) oilseeds: health attributes and food applications. Springer Singapore: Singapore, pp 351–371 |
| [183] |
|
| [184] |
|
| [185] |
Vasilakis G, Roidouli C, Karayannis D, Giannakis N, Rondags E, Chevalot I, Papanikolaou S (2024) Study of different parameters affecting production and productivity of polyunsaturated fatty acids (PUFAs) and gamma-Linolenic acid (GLA) by Cunninghamella elegans through glycerol conversion in shake flasks and bioreactors. Microorganisms 12 (10):2097-2115 |
| [186] |
|
| [187] |
|
| [188] |
|
| [189] |
|
| [190] |
|
| [191] |
|
| [192] |
|
| [193] |
|
| [194] |
|
| [195] |
|
| [196] |
|
| [197] |
|
| [198] |
|
| [199] |
|
| [200] |
|
| [201] |
|
| [202] |
|
| [203] |
|
| [204] |
|
| [205] |
|
| [206] |
|
| [207] |
|
| [208] |
|
| [209] |
|
| [210] |
|
| [211] |
|
| [212] |
|
| [213] |
|
| [214] |
|
| [215] |
|
| [216] |
|
| [217] |
|
| [218] |
|
| [219] |
|
| [220] |
|
| [221] |
|
| [222] |
|
| [223] |
|
| [224] |
|
| [225] |
|
| [226] |
|
| [227] |
|
| [228] |
|
| [229] |
|
| [230] |
Zikic V, Paunovic M, Milovic-Kovacevic M, Vucic V, Ristic-Medic D (2025) Nutrigenetics and omega-3 and gamma-Linolenic acid intake and status in patients with cancer: a PRISMA scoping review of research trends and challenges. Int J Mol Sci 26 (10):6038-6062 |
The Author(s)
/
| 〈 |
|
〉 |