| Summary: | Linolenic acid (LA) is gaining more interest within the scientific community. This is because it has a potential medical role in reducing the risk of inflammation, carcinogenesis, atherosclerosis and diabetes and is a valuable nutraceutical for human health. The oleaginous fungus <i>Mucor circinelloides</i> produces a high lipid content (36%), including valuable polyunsaturated fatty acids (PUFAs). However, the critical step in which oleic acid (OA) is converted into LA is not efficient at supplying enough substrates for PUFA synthesis. Hence, we propose a method to increase LA production based on genetic engineering. The overexpression of the Δ12-desaturase gene from <i>M. circinelloides</i> and <i>Mortierella alpina</i> increased the LA content and improved the lipid accumulation (from 14.9% to 21.6% in the Δ12-desaturase gene of the <i>M. circinelloides</i> overexpressing strain (Mc-D12MC) and from 14.9% to 18.7% in the Δ12-desaturase gene of <i>M. alpina</i> overexpressing strain (Mc-D12MA)). Additionally, the up-regulated expression levels of these genes targeted the genes involved in NADPH production, implying that the elevated Δ12-desaturase gene may function as a critical regulator of NADPH and lipid synthesis in <i>M. circinelloides</i>. This study provides the first evidence to support the design of metabolic engineering related to LA and PUFA production in <i>M. circinelloides</i> for potential industrial applications.
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