Synechococcus elongatus PCC 7942 as a Platform for Bioproduction of Omega-3 Fatty Acids

Abstract

Alpha-linolenic acid and stearidonic acid are precursors of omega-3 polyunsaturated fatty acids, essential nutrients in the human diet. The ability of cyanobacteria to directly convert atmospheric carbon dioxide into bio-based compounds makes them promising microbial chassis to sustainably produce omega-3 fatty acids. However, their potential in this area remains unexploited, mainly due to important gaps in our knowledge of fatty acid synthesis pathways. To gain insight into the cyanobacterial fatty acid biosynthesis pathways, we analyzed two enzymes involved in the elongation cycle, FabG and FabZ, in Synechococcus elongatus PCC 7942. Overexpression of these two enzymes led to an increase in C18 fatty acids, key intermediates in omega-3 fatty acid production. Nevertheless, coexpression of these enzymes with desaturases DesA and DesB from Synechococcus sp. PCC 7002 did not improve alpha-linolenic acid production, possibly due to their limited role in fatty acid synthesis. In any case, efficient production of stearidonic acid was not achieved by cloning DesD from Synechocystis sp. PCC 6803 in combination with the aforementioned DesA and DesB, reaching maximum production at 48 h post induction. According to current knowledge, this is the first report demonstrating that S. elongatus PCC 7942 can be used as an autotrophic chassis to produce stearidonic acid.

Solid-state fermentation produces greater stearidonic acid levels in genetically engineered Mucor circinelloides

“…Maximum production of SDA of Synechococcus elongatus PCC 7942 was up to 14·8% of its TFA content at 48 h by cloning multiple fatty acid synthase and desaturases (Santos‐Merino et al . 2022). A cyanobacterium Synechococcus sp.…”

“…Microbial fermentation processes have also been considered as viable methods for the commercial production of SDA. Maximum production of SDA of Synechococcus elongatus PCC 7942 was up to 14Á8% of its TFA content at 48 h by cloning multiple fatty acid synthase and desaturases (Santos-Merino et al 2022). A cyanobacterium Synechococcus sp.…”

Genomic analysis and biochemical profiling of an unaxenic strain of Synechococcus sp. isolated from the Peruvian Amazon Basin region

“…The pattern of fatty acid composition characterized by a high content of C16:0 and C16:1 n-7 fatty acids and low content of PUFAs is common in several cyanobacterial genera. These genera include Anabaena and Nostoc ( Caudales and Wells, 1992 ; Guedes et al, 2011 ), Cyanobacterium ( Sarsekeyeva et al, 2014 ), Dermocarpa , Dermocarpella , Myxosarcina , Pleurocapsa , Xenococcus ( Caudales et al, 2000 ), Aphanothece , Oscillatoria , Plectonema , Phormidium ( Oren et al, 1985 ), and Synechococcus ( Murata et al, 1992 ; Takeyama et al, 1997 ; Yu et al, 2000 ; Santos-Merino et al, 2022 ). Consequently, these cyanobacteria do not produce the high-demanded polyunsaturated fatty acids EPA and DHA.…”

“…Furthermore, both saturated fatty acids are chemically modified by the sequential action of desaturases and elongases. Consequently, depending on the gene pool contained in the genome that codes desaturases and elongases, the cyanobacterium will have the metabolic competence to biosynthesize or not a group of short-chain and/or long-chain PUFAs ( Ratledge, 2004 ; Poole et al, 2020 ; Santos-Merino et al, 2022 ).…”

“…Finally, several cyanobacteria are genetically transformable. The genetic transformability of these microorganisms can broaden their spectrum of biotechnological uses ( Jaiswal et al, 2018 ; Jaiswal et al, 2020 ; Purdy et al, 2022 ; Santos-Merino et al, 2022 ; Tan et al, 2022 ).…”