Shanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Ottawa Institute of Systems Biology and Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Nat Commun. 2020 Aug 17;11(1):4120. doi: 10.1038/s41467-020-17916-9.
Lysine acetylation (Kac), an abundant post-translational modification (PTM) in prokaryotes, regulates various microbial metabolic pathways. However, no studies have examined protein Kac at the microbiome level, and it remains unknown whether Kac level is altered in patient microbiomes. Herein, we use a peptide immuno-affinity enrichment strategy coupled with mass spectrometry to characterize protein Kac in the microbiome, which successfully identifies 35,200 Kac peptides from microbial or human proteins in gut microbiome samples. We demonstrate that Kac is widely distributed in gut microbial metabolic pathways, including anaerobic fermentation to generate short-chain fatty acids. Applying to the analyses of microbiomes of patients with Crohn's disease identifies 52 host and 136 microbial protein Kac sites that are differentially abundant in disease versus controls. This microbiome-wide acetylomic approach aids in advancing functional microbiome research.
赖氨酸乙酰化（Kac）是原核生物中一种丰富的翻译后修饰（PTM），可调节各种微生物代谢途径。然而，目前尚无研究在微生物组水平上检测蛋白质 Kac，也不清楚 Kac 水平是否在患者微生物组中发生改变。在此，我们使用肽免疫亲和富集策略结合质谱法来表征微生物组中的蛋白质 Kac，该策略成功地从肠道微生物组样本中的微生物或人类蛋白中鉴定出 35200 个 Kac 肽。我们证明 Kac 广泛分布于肠道微生物代谢途径中，包括厌氧发酵以产生短链脂肪酸。将该方法应用于克罗恩病患者的微生物组分析，鉴定出 52 个宿主和 136 个微生物蛋白 Kac 位点，这些位点在疾病与对照中丰度存在差异。这种全微生物组乙酰组学方法有助于推进功能微生物组研究。
