Acyl-lipid desaturases and Vipp1 cooperate in cyanobacteria to produce novel omega-3 PUFA-containing glycolipids

Leslie B Poole; Derek Parsonage; Susan Sergeant; Leslie R Miller; Jingyun Lee; Cristina M Furdui; Floyd H Chilton

doi:10.1186/s13068-020-01719-7

Acyl-lipid desaturases and Vipp1 cooperate in cyanobacteria to produce novel omega-3 PUFA-containing glycolipids

Biotechnol Biofuels. 2020 May 6:13:83. doi: 10.1186/s13068-020-01719-7. eCollection 2020.

Authors

Leslie B Poole^{1

2}, Derek Parsonage^{1

2}, Susan Sergeant¹, Leslie R Miller^{3

4}, Jingyun Lee^{5

6}, Cristina M Furdui^{2

5

6}, Floyd H Chilton^{3

6

7}

Affiliations

¹ 1Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157 USA.
² 2Center for Redox Biology and Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157 USA.
³ 3Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157 USA.
⁴ Present Address: 139 N St. Patrick St., New Orleans, LA 70119 USA.
⁵ 4Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157 USA.
⁶ 5Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157 USA.
⁷ 6Department of Nutritional Sciences and the BIO5 Institute, University of Arizona, Tucson, AZ USA.

Abstract

Background: Dietary omega-3 (n-3), long chain (LC-, ≥ 20 carbons), polyunsaturated fatty acids (PUFAs) derived largely from marine animal sources protect against inflammatory processes and enhance brain development and function. With the depletion of natural stocks of marine animal sources and an increasing demand for n-3 LC-PUFAs, alternative, sustainable supplies are urgently needed. As a result, n-3 18-carbon and LC-PUFAs are being generated from plant or algal sources, either by engineering new biosynthetic pathways or by augmenting existing systems.

Results: We utilized an engineered plasmid encoding two cyanobacterial acyl-lipid desaturases (DesB and DesD, encoding Δ15 and Δ6 desaturases, respectively) and "vesicle-inducing protein in plastids" (Vipp1) to induce production of stearidonic acid (SDA, 18:4 n-3) at high levels in three strains of cyanobacteria (10, 17 and 27% of total lipids in Anabaena sp. PCC7120, Synechococcus sp. PCC7002, and Leptolyngbya sp. strain BL0902, respectively). Lipidomic analysis revealed that in addition to SDA, the rare anti-inflammatory n-3 LC-PUFA eicosatetraenoic acid (ETA, 20:4 n-3) was synthesized in these engineered strains, and ~ 99% of SDA and ETA was complexed to bioavailable monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) species. Importantly, novel molecular species containing alpha-linolenic acid (ALA), SDA and/or ETA in both acyl positions of MGDG and DGDG were observed in the engineered Leptolyngbya and Synechococcus strains, suggesting that these could provide a rich source of anti-inflammatory molecules.

Conclusions: Overall, this technology utilizes solar energy, consumes carbon dioxide, and produces large amounts of nutritionally important n-3 PUFAs and LC-PUFAs. Importantly, it can generate previously undescribed, highly bioavailable, anti-inflammatory galactosyl lipids. This technology could therefore be transformative in protecting ocean fisheries and augmenting the nutritional quality of human and animal food products.

Keywords: Aquaculture; Bioengineering; Cyanobacteria; Leptolyngbya; Nutrition; Omega-3 polyunsaturated fatty acids.

Abstract

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