초록
<P>NADPH is known to be a key cofactor required for fatty acid synthesis and desaturation. Various enzymatic reactions can generate NADPH. To determine the effect of NADPH sources on lipogenesis, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (PGD), isocitrate dehydrogenase (IDH), and malic enzyme (ME) were overexpressed in <I>Mortierella alpina</I>. Our results showed that G6PD2 had the most significant effect on fatty acid synthesis, with a 1.7-fold increase in total fatty acid, whereas ME2 was more effective in desaturation, with a 1.5-fold increase in arachidonic acid (AA) content over control. Co-overexpression of G6PD2 and ME2 improved both fatty acid synthesis and desaturation. Within 96 h of fermentation using the fed-batch method, the co-overexpressing strain accumulated AA at a productivity of 1.9 ± 0.2 g/(liter · day), which was 7.2-fold higher than that in the <I>M. alpina</I> control that was cultured in a flask.</P><P><B>IMPORTANCE</B> This study proved that the pentose phosphate pathway is the major NADPH contributor during fatty acid synthesis in <I>M. alpina</I>. The NADPH sources may be differently responsible for fatty acid synthesis or desaturation. Co-overexpression of G6PD2 and ME2 significantly increases AA production.</P>