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Background <p><i>Yarrowia lipolytica</i> is a promising host for sustainable microbial oil production from waste-derived carboxylic acids such as acetate and propionate. Nonetheless, the molecular mechanisms underlying the metabolism and assimilation of these substrates, particularly under nitrogen limitation, are still not fully understood.</p> Results <p>We conducted a multi-condition transcriptomic analysis of <i>Y. lipolytica</i> strain EXF-17398 under nitrogen-limiting conditions to investigate its transcriptional adaptation to acetate and propionate utilisation. Our results revealed distinct transcriptional responses associated with metabolic adaptation, including the coordinated regulation of Jen and Gpr carboxylate transporter families, suggesting a dual system for carboxylate uptake. <i>JEN5</i> and <i>GPR1</i> appear central to propionate and acetate utilisation, respectively. Our data suggest that propionate toxicity is mitigated through its conversion via the methylcitrate cycle and potentially the malonate semialdehyde pathway, preventing accumulation of cytotoxic propionyl-CoA in the cytosol. The upregulation of carnitine acyltransferases suggests active mitochondrial transport of acyl-CoAs, linking detoxification with energy metabolism. Under tested conditions, the de novo lipid synthesis was consistent with carbon overflow from acetyl-CoA and propionyl-CoA, supported by intracellular nitrogen recycling and redox balancing, independent of classical nitrogen regulatory pathways.</p> Conclusions <p>These findings illustrate the capacity of <i>Y. lipolytica</i> to coordinate carbon and nitrogen metabolism during carboxylate utilisation, such as acetate and propionate, offering insights to guide the optimisation of microbial oil production from renewable feedstocks.</p>

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Transcriptomics-based analysis of acetate and propionate transport and metabolism in Yarrowia lipolytica

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月10日

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  • Mia Žganjar,
  • David Sanz-Mata,
  • Urška Hancman,
  • Neža Čadež,
  • Cene Gostinčar,
  • Cristina González-Fernández,
  • Elia Tomás-Pejó,
  • Uroš Petrovič

摘要

Background

Yarrowia lipolytica is a promising host for sustainable microbial oil production from waste-derived carboxylic acids such as acetate and propionate. Nonetheless, the molecular mechanisms underlying the metabolism and assimilation of these substrates, particularly under nitrogen limitation, are still not fully understood.

Results

We conducted a multi-condition transcriptomic analysis of Y. lipolytica strain EXF-17398 under nitrogen-limiting conditions to investigate its transcriptional adaptation to acetate and propionate utilisation. Our results revealed distinct transcriptional responses associated with metabolic adaptation, including the coordinated regulation of Jen and Gpr carboxylate transporter families, suggesting a dual system for carboxylate uptake. JEN5 and GPR1 appear central to propionate and acetate utilisation, respectively. Our data suggest that propionate toxicity is mitigated through its conversion via the methylcitrate cycle and potentially the malonate semialdehyde pathway, preventing accumulation of cytotoxic propionyl-CoA in the cytosol. The upregulation of carnitine acyltransferases suggests active mitochondrial transport of acyl-CoAs, linking detoxification with energy metabolism. Under tested conditions, the de novo lipid synthesis was consistent with carbon overflow from acetyl-CoA and propionyl-CoA, supported by intracellular nitrogen recycling and redox balancing, independent of classical nitrogen regulatory pathways.

Conclusions

These findings illustrate the capacity of Y. lipolytica to coordinate carbon and nitrogen metabolism during carboxylate utilisation, such as acetate and propionate, offering insights to guide the optimisation of microbial oil production from renewable feedstocks.