The interplay of transcriptional regulator SREBP1 with AMPK promotes lipid biosynthesis in Mucor circinelloides WJ11

SREBP1 is a transcription factor that influences lipogenesis by regulating key genes associated with lipid biosynthesis, while AMPK, modulates lipid metabolism by regulating acetyl-CoA carboxylase. The exact role of these metabolic regulators in oleaginous microbes remains unclear. This study identified and manipulated the genes encoding SREBP1 (sre1) and α1 subunit of AMPK (ampk-α1) in Mucor circinelloides WJ11. Individual overexpression of sre1 yielded 32.5 % lipids and 21 g/L biomass, while ampk-α1 deletion combined with sre1 overexpression yielded 42.5 % lipids and 25 g/L biomass in mutant strains. This increase correlated with upregulated expression of key lipogenic genes and enzyme activity, enhancing lipid production and biomass. These surges were correlated with the increased mRNA levels of key genes (acl, acc1, acc2, cme1, fas1, g6pdh1, g6pdh2 and 6pgdh2). Enzyme activity analysis further showed that upregulation of ACL, ACC, ME, FAS, G6PDH and 6PGDH might provide more precursors and NADPH for lipid biosynthesis in sre1 overexpressing strains. Conversely, the activities of these genes and enzymes were markedly downregulated in sre1 deleted mutants consistent with lower lipid production and biomass than the control. These findings open new avenues for research by exploring the coordinated role of sre1 and ampk-α1 in lipid metabolism in M. circinelloides.