Kog1 Represses Lipid Accumulation in Mucor circinelloides: A Transcriptomic Analysis Across Nitrogen Conditions

Area of Science:

• Microbiology and Biotechnology
• Molecular Biology
• Metabolic Engineering

Background:

• Oleaginous microorganisms accumulate lipids under specific nutrient conditions.
• The target of rapamycin complex 1 (TORC1) pathway is crucial for lipid accumulation.
• Kog1, a TORC1 component, was previously found to negatively regulate lipid accumulation in *Mucor circinelloides*.

Purpose of the Study:

• To investigate the role of Kog1 in regulating lipid accumulation in *Mucor circinelloides*.
• To analyze the transcriptomic differences between Kog1 knockout and control strains.
• To understand the metabolic reprogramming induced by Kog1 knockout.

Main Methods:

• Construction and analysis of a Kog1 knockout strain of *Mucor circinelloides*.
• Transcriptomic analysis under nitrogen-limited and nitrogen-sufficient conditions.
• Measurement of cell dry weight and lipid content.

Main Results:

• Kog1 knockout significantly decreased cell dry weight but increased lipid content.
• Upregulation of genes involved in the glyoxylic acid cycle and key lipid synthesis enzymes (ACC, FAS, Δ9 desaturase).
• Activation of the pyruvate-acetaldehyde-acetate metabolic axis and altered branched-chain amino acid metabolism, redirecting carbon flux towards acetyl-CoA.
• Significant upregulation of the SSK1p transcription factor, involved in nutrient stress response.

Conclusions:

• Kog1 negatively regulates lipid accumulation in *Mucor circinelloides*.
• Kog1 knockout enhances lipid metabolism and redirects carbon flux from amino acid synthesis to lipid production.
• The SSK1p transcription factor plays a role in the nutrient stress response triggered by Kog1 deletion.