Overexpression of the Mitochondrial Malic Enzyme Genes (malC and malD) Improved the Lipid Accumulation in Mucor circinelloides WJ11

Abstract

Mucor circinelloides serves as a model organism to investigate the lipid metabolism in oleaginous microorganisms. It is considered as an important producer of γ-linolenic acid (GLA) that has vital medicinal benefits. In this study, we used WJ11, a high lipid-producing strain of M. circinelloides (36% w/w lipid, cell dry weight, CDW), to examine the role in lipid accumulation of two mitochondrial malic enzyme (ME) genes malC and malD. The homologous overexpression of both malC and malD genes enhanced the total lipid content of WJ11 by 41.16 and 32.34%, respectively. In parallel, the total content of GLA was enhanced by 16.73 and 46.76% in malC and malD overexpressing strains, respectively, because of the elevation of total lipid content. The fact that GLA content was enhanced more in the strain with lower lipid content increase and vice versa, indicated that engineering of mitochondrial MEs altered the fatty acid profile. Our results reveal that mitochondrial ME plays an important role in lipid metabolism and suggest that future approaches may involve simultaneous overexpression of distinct ME genes to boost lipid accumulation even further.

AoMae1 Regulates Hyphal Fusion, Lipid Droplet Accumulation, Conidiation, and Trap Formation in Arthrobotrys oligospora

“…MDH further influences the synthesis and degradation of compounds by affecting the TCA cycle or the glyoxylate cycle. Examples include Mucor circinelloides WJ11, in which overexpression of the mitochondrial malic enzyme genes (malC and malD) improves lipid accumulation [7], and the glyoxylate cycle gene icl1, which is essential for the metabolic flexibility and pathogenicity of Candida glabrata [8]. The amino acid sequence similarity of the primary structure of MDH from different sources is minor, but the coenzyme binding, nucleotide binding, and catalytic active sites are particularly well conserved.…”