Skip to main content
SpringerLink
Log in

Lipid accumulation and SNF1 transcriptional analysis of Mucor circinelloides on xylose under nitrogen limitation

  • Original Paper
  • Published:
Antonie van Leeuwenhoek Aims and scope Submit manuscript

Abstract

Sucrose non-fermenting 1 (SNF1) plays a crucial role in utilizing non-glucose carbon sources and regulating lipid metabolism. However, the mechanism by which SNF1 regulates lipid accumulation in oleaginous filamentous fungi in response to nutrient signals remains unclear. In the present study, by analysing the growth and lipid accumulation of M. circinelloides on xylose under nitrogen limitation, combined with the transcriptional changes of each subunit of SNF1, the regulation of SNF1 between nutrient signal and lipid accumulation was explored. The results showed that with the increase of carbon/nitrogen (C/N) ratio, the xylose consumption and cell growth of M. circinelloides decreased, and the lipid accumulation increased gradually. The optimal C/N ratio was 160:1, and the maximum lipid yield was 4.1 g/L. Two subunits of SNF1, Snf-α1 and Snf-β, are related to the regulation of lipid metabolism in response to nutrient signals from different external nitrogen sources. This is the first report on the transcriptional analysis of SNF1 subunits on xylose metabolism under nitrogen limitation. This study provides a basis for further understanding of lipid synthesis mechanism on xylose in oleaginous fungi, and it also lays a foundation for the genetic engineering of high-lipid strain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aslam M, Ladilov Y (2022) Emerging Role of cAMP/AMPK signaling. Cells 11:308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertram PG, Choi JH, Carvalho J, Chan TF, Ai W, Zheng XF (2002) Convergence of TOR-nitrogen and Snf1-glucose signaling pathways onto Gln3. Mol Cell Biol 22:1246–1252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvalho AKF, Bento HBS, Rivaldi JD, De Castro HF (2018) Direct transesterification of Mucor circinelloides biomass for biodiesel production: effect of carbon sources on the accumulation of fungal lipids and biofuel properties. Fuel 234:789–796

    Article  CAS  Google Scholar 

  • Chu L, Zan X, Tang X, Zhao L, Chen H, Chen YQ, Chen W, Song Y (2016) The role of a xylose isomerase pathway in the conversion of xylose to lipid in Mucor circinelloides. RSC Adv 6:77944–77952

    Article  CAS  Google Scholar 

  • Fazili ABA, Shah AM, Zan X, Naz T, Nosheen S, Nazir Y, Ullah S, Zhang H, Song Y (2022) Mucor circinelloides: a model organism for oleaginous fungi and its potential applications in bioactive lipid production. Microb Cell Fact 21:29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferreira JA, Taherzadeh MJ (2020) Improving the economy of lignocellulose-based biorefineries with organosolv pretreatment. Bioresour Technol 299:122695

    Article  CAS  PubMed  Google Scholar 

  • Ghillebert R, Swinnen E, Wen J, Vandesteene L, Ramon M, Norga K, Rolland F, Winderickx J (2011) The AMPK/SNF1/SnRK1 fuel gauge and energy regulator: structure, function and regulation. FEBS J 278:3978–3990

    Article  CAS  PubMed  Google Scholar 

  • Gnoni A, Di Chiara Stanca B, Giannotti L, Gnoni GV, Siculella L, Damiano F (2022) Quercetin reduces lipid accumulation in a cell model of NAFLD by inhibiting de novo fatty acid synthesis through the acetyl-CoA carboxylase 1/AMPK/PP2A axis. Int J Mol Sci 23:1044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou J, Qiu C, Shen Y, Li H, Bao X (2017) Engineering of saccharomyces cerevisiae for the efficient co-utilization of glucose and xylose. FEMS Yeast Res 17(4):1–11

  • Jeon SM, Chandel NS, Hay N (2012) AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485:661–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin M, Slininger PJ, Dien BS, Waghmode S, Moser BR, Orjuela A, Sousa Lda C, Balan V (2015) Microbial lipid-based lignocellulosic biorefinery: feasibility and challenges. Trends Biotechnol 33:43–54

    Article  CAS  PubMed  Google Scholar 

  • Jo S, Yoon J, Lee SM, Um Y, Han SO, Woo HM (2017) Modular pathway engineering of Corynebacterium glutamicum to improve xylose utilization and succinate production. J Biotechnol 258:69–78

    Article  CAS  PubMed  Google Scholar 

  • Kang NK, Lee JW, Ort DR, Jin YS (2022) L-malic acid production from xylose by engineered Saccharomyces cerevisiae. Biotechnol J 17:e2000431

    Article  PubMed  Google Scholar 

  • Kong Y, Zhao C, Tan P, Liu S, Huang Y, Zeng F, Ma P, Guo Y, Zhao B, Wang J (2022) FGF21 reduces lipid accumulation in bovine hepatocytes by enhancing lipid oxidation and reducing lipogenesis via AMPK signaling. Animals (basel) 12:939

    Article  PubMed  Google Scholar 

  • Nosheen S et al (2021a) Role of Snf-beta in lipid accumulation in the high lipid-producing fungus Mucor circinelloides WJ11. Microb Cell Fact 20:52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nosheen S, Yang J, Naz T, Nazir Y, Ahmad MI, Fazili ABA, Li S, Mustafa K, Song Y (2021b) Annotation of AMP-activated protein kinase genes and its comparative transcriptional analysis between high and low lipid producing strains of Mucor circinelloides. Biotechnol Lett 43:193–202

    Article  CAS  PubMed  Google Scholar 

  • Palazzolo MA, Garcia-Perez M (2022) Microbial lipid biosynthesis from lignocellulosic biomass pyrolysis products. Biotechnol Adv 54:107791

    Article  CAS  PubMed  Google Scholar 

  • Polge C, Thomas M (2007) SNF1/AMPK/SnRK1 kinases, global regulators at the heart of energy control? Trends Plant Sci 12:20–28

    Article  CAS  PubMed  Google Scholar 

  • Raab AM, Hlavacek V, Bolotina N, Lang C (2011) Shifting the fermentative/oxidative balance in Saccharomyces cerevisiae by transcriptional deregulation of Snf1 via overexpression of the upstream activating kinase Sak1p. Appl Environ Microbiol 77:1981–1989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ratledge C, Wynn JP (2002) The biochemistry and molecular biology of lipid accumulation in oleaginous microorganisms. Adv Appl Microbiol 51:1–51

    Article  CAS  PubMed  Google Scholar 

  • Sanz P, Viana R, Garcia-Gimeno MA (2016) AMPK in yeast: the SNF1 (Sucrose non-fermenting 1) protein kinase complex. Exp Suppl 107:353–374

    CAS  PubMed  Google Scholar 

  • Seip J, Jackson R, He H, Zhu Q, Hong SP (2013) Snf1 is a regulator of lipid accumulation in Yarrowia lipolytica. Appl Environ Microbiol 79:7360–7370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi S, Chen Y, Siewers V, Nielsen J (2014) Improving production of malonyl coenzyme A-derived metabolites by abolishing Snf1-dependent regulation of Acc1. nBio 5:e01130-e1114

    Google Scholar 

  • Straathof AJ, van Gulik WM (2012) Production of fumaric acid by fermentation. Subcell Biochem 64:225–240

    Article  CAS  PubMed  Google Scholar 

  • Tang X, Zhao L, Chen H, Chen YQ, Chen W, Song Y, Ratledge C (2015) Complete genome sequence of a high lipid-producing strain of Mucor circinelloides WJ11 and comparative genome analysis with a low lipid-producing strain CBS 277.49. PLoS ONE 10:e0137543

    Article  PubMed  PubMed Central  Google Scholar 

  • Tate JJ, Cooper TG (2007) Stress-responsive Gln3 localization in Saccharomyces cerevisiae is separable from and can overwhelm nitrogen source regulation. J Biol Chem 282:18467–18480

    Article  CAS  PubMed  Google Scholar 

  • Usaite R, Jewett MC, Oliveira AP, Yates JR 3rd, Olsson L, Nielsen J (2009) Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator. Mol Syst Biol 5:319

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang L, Zhang H, Zhang Y, Song Y (2019) (13)C metabolic flux analysis on roles of malate transporter in lipid accumulation of Mucor circinelloides. Microb Cell Fact 18:154

    Article  PubMed  PubMed Central  Google Scholar 

  • Woods A, Munday MR, Scott J, Yang X, Carlson M, Carling D (1994) Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. J Biol Chem 269:19509–19515

    Article  CAS  PubMed  Google Scholar 

  • Wynn JP, Hamid AA, Li Y, Ratledge C (2001) Biochemical events leading to the diversion of carbon into storage lipids in the oleaginous fungi Mucor circinelloides and Mortierella alpina. Microbiology (reading) 147:2857–2864

    Article  CAS  PubMed  Google Scholar 

  • Yu Y, Xu Z, Chen S, Jin M (2020) Microbial lipid production from dilute acid and dilute alkali pretreated corn stover via Trichosporon dermatis. Bioresour Technol 295:122253

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Song Y (2021) Lipid accumulation by xylose metabolism engineered Mucor circinelloides strains on corn straw hydrolysate. Appl Biochem Biotechnol 193:856–868

    Article  PubMed  Google Scholar 

  • Zhang Y, Wang Y, Yang J, Yang W, Wang X, Wu C, Song Y (2022) Improved gamma-Linolenic acid production from cellulose in Mucor circinelloides via coexpression of cellobiohydrolase and delta-6 desaturase. J Agric Food Chem 70:4373–4381

    Article  CAS  PubMed  Google Scholar 

  • Zhu Z et al (2012) A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides. Nat Commun 3:1112

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Shandong Provincial Natural Science Foundation (ZR2020MC007), the National Natural Science Foundation of China (32101927), School-City integration project in Zhangdian District (2021JSCG0016).

Author information

Authors and Affiliations

  1. Food Bioengineering and Technology Laboratory, Department of Food Science and Nutrition, College of Culture and Tourism, University of Jinan, 13 Shungeng Road, Jinan, 250022, People’s Republic of China

    Yao Zhang

  2. Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, 266 Xincun West Road, Zibo, 255000, People’s Republic of China

    Yao Zhang, Yueping Yang, Silu Zhang, Qing Liu, Wenrui Dang & Yuanda Song

Authors
  1. Yao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yueping Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenrui Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuanda Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YZ was involved in the study conception, experimental design, data analysis, figures and tables’ arrangement, result interpretation, manuscript writing and review of the final draft. YY and SZ carried out the experiments and collected data. QL and WD participated in the experimental research. YS conceived the study and reviewed the original manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yao Zhang.

Ethics declarations

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 39 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Yang, Y., Zhang, S. et al. Lipid accumulation and SNF1 transcriptional analysis of Mucor circinelloides on xylose under nitrogen limitation. Antonie van Leeuwenhoek 116, 383–391 (2023). https://doi.org/10.1007/s10482-023-01810-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10482-023-01810-7

Keywords

Search

Navigation