Santos-Merino María, Gutiérrez-Lanza Raquel, Nogales Juan, García José Luis, de la Cruz Fernando
Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-CSIC, 39011 Santander, Spain.
Department of Systems Biology, Centro Nacional de Biotecnología (CSIC), 28049 Madrid, Spain.
Life (Basel). 2022 May 29;12(6):810. doi: 10.3390/life12060810.
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 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 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 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 PCC 7942 can be used as an autotrophic chassis to produce stearidonic acid.
α-亚麻酸和硬脂酸是ω-3多不饱和脂肪酸的前体，而ω-3多不饱和脂肪酸是人类饮食中的必需营养素。蓝细菌能够将大气中的二氧化碳直接转化为生物基化合物，这使其成为可持续生产ω-3脂肪酸的有前景的微生物底盘。然而，它们在这一领域的潜力尚未得到开发，主要是因为我们对脂肪酸合成途径的了解存在重大空白。为了深入了解蓝细菌脂肪酸生物合成途径，我们分析了集胞藻PCC 7942中参与延长循环的两种酶，即FabG和FabZ。这两种酶的过表达导致C18脂肪酸增加，而C18脂肪酸是ω-3脂肪酸生产中的关键中间体。然而，将这些酶与来自聚球藻PCC 7002的去饱和酶DesA和DesB共表达并没有提高α-亚麻酸的产量，这可能是因为它们在脂肪酸合成中的作用有限。无论如何，通过克隆来自聚球藻PCC 6803的DesD并与上述DesA和DesB组合，并未实现硬脂酸的高效生产，诱导后48小时达到最大产量。根据目前的知识，这是第一份证明集胞藻PCC 7942可作为自养底盘生产硬脂酸的报告。
