中国科学院微生物所陈义华等合作近期取得重要工作进展，他们研究提出β-d-manno-heptoses（β-d-甘露庚糖）是跨物种的免疫激动剂。相关研究成果2024年8月9日在线发表于《科学》杂志上。
据介绍，细菌的小分子代谢物，如腺苷-二磷酸-d-甘油-β-d-甘露-庚糖（ADP- heptose）及其衍生物，是哺乳动物有效的先天免疫激动剂。
研究人员发现，功能性核苷酸-二磷酸-庚糖生物合成酶（HBE）广泛分布于细菌、古菌、真核生物和病毒中。研究人员确定了保守的STTR5基序作为庚糖核苷酸转移酶的标志，该酶不仅能合成ADP- heptose，还能合成胞苷二磷酸（CDP）和尿苷二磷酸（UDP）-heptose。
CDP和UDP-heptose都是激动剂，在人类和小鼠细胞以及小鼠中引发比ADP-heptose更强的α-蛋白激酶1（ALPK1）依赖的免疫反应。研究人员还在古菌中生产了ADP-heptose，并验证了其先天免疫激动剂功能。
因此，β-d-甘露庚糖是一种跨物种的小分子病原体相关分子模式，可激活 ALPK1 依赖性先天免疫信号级联。
附：英文原文
Title: The β-d-manno-heptoses are immune agonists across kingdoms
Author: Yue Tang, Xiaoying Tian, Min Wang, Yinglu Cui, Yang She, Zhaoxiang Shi, Jiaqi Liu, Huijin Mao, Lilu Liu, Chao Li, Yuwei Zhang, Pengwei Li, Yue Ma, Jinyuan Sun, Qing Du, Jie Li, Jun Wang, De-feng Li, Bian Wu, Feng Shao, Yihua Chen
Issue&Volume: 2024-08-09
Abstract: Bacterial small molecule metabolites such as adenosine-diphosphate-d-glycero-β-d-manno-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STTR5 motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)– and uridine-diphosphate (UDP)–heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)–dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the β-d-manno-heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.
DOI: adk7314
Source: https://www.science.org/doi/10.1126/science.adk7314
来源：科学网 小柯机器人