A yeast-based tool for screening mammalian diacylglycerol acyltransferase inhibitors

IF 3.9 3区 生物学 Q2 MICROBIOLOGY MicrobiologyOpen Pub Date : 2022-12-01 DOI:10.1002/mbo3.1334
Peter Gajdoš, Rodrigo Ledesma-Amaro, Jean-Marc Nicaud, Tristan Rossignol
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Abstract

Dysregulation of lipid metabolism is associated with obesity and metabolic diseases but there is also increasing evidence of a relationship between lipid body excess and cancer. Lipid body synthesis requires diacylglycerol acyltransferases (DGATs) which catalyze the last step of triacylglycerol synthesis from diacylglycerol and acyl-coenzyme A. The DGATs and in particular DGAT2, are therefore considered potential therapeutic targets for the control of these pathologies. Here, the murine and the human DGAT2 were overexpressed in the oleaginous yeast Yarrowia lipolytica deleted for all DGAT activities, to evaluate the functionality of the enzymes in this heterologous host and DGAT activity inhibitors. This work provides evidence that mammalian DGATs expressed in Y. lipolytica are a useful tool for screening chemical libraries to identify potential inhibitors or activators of these enzymes of therapeutic interest.

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筛选哺乳动物二酰基甘油酰基转移酶抑制剂的酵母为基础的工具
脂质代谢失调与肥胖和代谢性疾病有关,但也有越来越多的证据表明脂质体过量与癌症之间存在关系。脂体合成需要二酰基甘油酰基转移酶(dgat),它催化二酰基甘油和酰基辅酶a合成三酰基甘油的最后一步。因此,dgat,特别是DGAT2,被认为是控制这些病理的潜在治疗靶点。在本研究中,小鼠和人类DGAT2在剔除所有DGAT活性的脂质耶氏酵母中过表达,以评估该酶在异种宿主和DGAT活性抑制剂中的功能。这项工作提供了证据,表明哺乳动物在脂肪瘤中表达的dgat是筛选化学文库的有用工具,可以识别这些酶的潜在抑制剂或激活剂。
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来源期刊
MicrobiologyOpen
MicrobiologyOpen MICROBIOLOGY-
CiteScore
8.00
自引率
0.00%
发文量
78
审稿时长
20 weeks
期刊介绍: MicrobiologyOpen is a peer reviewed, fully open access, broad-scope, and interdisciplinary journal delivering rapid decisions and fast publication of microbial science, a field which is undergoing a profound and exciting evolution in this post-genomic era. The journal aims to serve the research community by providing a vehicle for authors wishing to publish quality research in both fundamental and applied microbiology. Our goal is to publish articles that stimulate discussion and debate, as well as add to our knowledge base and further the understanding of microbial interactions and microbial processes. MicrobiologyOpen gives prompt and equal consideration to articles reporting theoretical, experimental, applied, and descriptive work in all aspects of bacteriology, virology, mycology and protistology, including, but not limited to: - agriculture - antimicrobial resistance - astrobiology - biochemistry - biotechnology - cell and molecular biology - clinical microbiology - computational, systems, and synthetic microbiology - environmental science - evolutionary biology, ecology, and systematics - food science and technology - genetics and genomics - geobiology and earth science - host-microbe interactions - infectious diseases - natural products discovery - pharmaceutical and medicinal chemistry - physiology - plant pathology - veterinary microbiology We will consider submissions across unicellular and cell-cluster organisms: prokaryotes (bacteria, archaea) and eukaryotes (fungi, protists, microalgae, lichens), as well as viruses and prions infecting or interacting with microorganisms, plants and animals, including genetic, biochemical, biophysical, bioinformatic and structural analyses. The journal features Original Articles (including full Research articles, Method articles, and Short Communications), Commentaries, Reviews, and Editorials. Original papers must report well-conducted research with conclusions supported by the data presented in the article. We also support confirmatory research and aim to work with authors to meet reviewer expectations. MicrobiologyOpen publishes articles submitted directly to the journal and those referred from other Wiley journals.
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