Shaoqi Li , Junhuan Yang , Hassan Mohamed , Xiuwen Wang , Wenyue Shi , Futing Xue , Sergio López-García , Qing Liu , Yuanda Song
{"title":"AMP deaminase: A crucial regulator in nitrogen stress and lipid metabolism in Mucor circinelloides","authors":"Shaoqi Li , Junhuan Yang , Hassan Mohamed , Xiuwen Wang , Wenyue Shi , Futing Xue , Sergio López-García , Qing Liu , Yuanda Song","doi":"10.1016/j.bbalip.2023.159434","DOIUrl":null,"url":null,"abstract":"<div><p><span>Lipid biosynthesis is a significant metabolic response to nitrogen starvation in oleaginous fungi. The oleaginous fungus </span><span><em>Mucor circinelloides</em></span><span><span> 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 </span>lipid synthesis in this </span><em>M. circinelloides</em>, we identified two genes (<em>ampd1</em> and <em>ampd2</em>) encoding AMPD and constructed an <em>ampd</em> double knockout mutant. The engineered <em>M. circinelloides</em><span><span><span> strain elevated cell growth and lipid accumulation, as well as the content of </span>oleic acid (OA) and gamma-linolenic acid (GLA). In addition to the expected increase in transcription levels of genes associated with lipid and </span>TAG<span><span><span> synthesis, we observed suppression of lipid degradation<span> 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 </span></span>nitrogen metabolism, including </span>nitrogen assimilation<span> and purine metabolism<span> (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 </span></span></span></span><em>M. circinelloides</em>, 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.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 2","pages":"Article 159434"},"PeriodicalIF":3.9000,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular and cell biology of lipids","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1388198123001580","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.