Lipid biosynthesis is a significant metabolic response to nitrogen starvation in oleaginous fungi. The oleaginous fungus Mucor circinelloides copes with nitrogen stress by degrading AMP through AMP deaminase (AMPD). However, the mechanism of AMPD in regulating lipogenesis remains largely unclear. To elucidate the mechanism of AMPD in lipid synthesis in this M. circinelloides, we identified two genes (ampd1 and ampd2) encoding AMPD and constructed an ampd double knockout mutant. The engineered M. circinelloides strain elevated cell growth and lipid accumulation, as well as the content of oleic acid (OA) and gamma-linolenic acid (GLA). In addition to the expected increase in transcription levels of genes associated with lipid and TAG synthesis, we observed suppression of lipid degradation and reduced amino acid biosynthesis. This suggested that the deletion of AMPD genes induces the redirection of carbon towards lipid synthesis pathways. Moreover, the pathways related to nitrogen metabolism, including nitrogen assimilation and purine metabolism (especially energy level), were also affected in order to maintain homeostasis. Further analysis discovered that the transcription factors (TFs) related to lipid accumulation were also regulated. This study provides new insights into lipid biosynthesis in M. circinelloides, indicating that the trigger for lipid accumulation is not entirely AMPD-dependent and suggest that there may be additional mechanisms involved in the initiation of lipogenesis.

脂质生物合成是产油真菌对氮饥饿的重要代谢反应。产油真菌卷枝毛霉通过 AMP 脱氨酶 (AMPD) 降解 AMP 来应对氮胁迫。然而，AMPD 调节脂肪生成的机制仍不清楚。为了阐明AMPD在卷绕M. circinelloides中脂质合成的机制，我们鉴定了编码AMPD的两个基因（ ampd1和ampd2 ）并构建了ampd双敲除突变体。改造后的M. circinelloides菌株提高了细胞生长和脂质积累，以及油酸 (OA) 和 γ-亚麻酸 (GLA) 的含量。除了与脂质和TAG合成相关的基因转录水平预期增加之外，我们还观察到脂质降解的抑制和氨基酸生物合成的减少。这表明 AMPD 基因的缺失会诱导碳转向脂质合成途径。此外，与氮代谢相关的途径，包括氮同化和嘌呤代谢（尤其是能量水平）也受到影响，以维持体内平衡。进一步分析发现，与脂质积累相关的转录因子（TF）也受到调节​​。这项研究提供了关于M. circinelloides脂质生物合成的新见解，表明脂质积累的触发因素并不完全依赖于 AMPD，并表明可能存在其他机制参与脂肪生成的启动。