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

Naz T 1 , Zhao XY 2 , Li S 3 , Saeed T 4 , Ullah S 5 , Nazir Y 6 Show all authors , Liu Q 7 , Mohamed H 8 , Song Y 9

Affiliations 

  • 1 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China; State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, Shandong 271018, China
  • 2 State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, Shandong 271018, China. Electronic address: zhxy@sdau.edu.cn
  • 3 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China
  • 4 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China; Department of Diet and Nutritional Sciences, Ibadat International University, Islamabad 45750, Pakistan. Electronic address: tariqsaeed@sdut.edu.cn
  • 5 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China; University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore 54000, Pakistan
  • 6 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China; Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia
  • 7 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China. Electronic address: qingliu0906@sdut.edu.cn
  • 8 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China; Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt. Electronic address: hassanmohamed85@azhar.edu.eg
  • 9 Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China. Electronic address: ysong@sdut.edu.cn
Biochim Biophys Acta Mol Cell Biol Lipids, 2025 Mar;1870(2):159592.
PMID: 39733936 DOI: 10.1016/j.bbalip.2024.159592

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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