美国国立环境卫生研究所Xiaoling Li和Igor Shats研究小组合作研究有了新进展。他们发现细菌通过去酰胺生物合成途径促进其哺乳动物宿主烟酰胺腺嘌呤二核苷酸（NAD）代谢。这一研究成果发表在2020年3月5日出版的《细胞-代谢》杂志上。

在该研究中，研究人员发现了细菌和哺乳动物细胞之间意想不到的跨界合作，其中细菌有助于宿主NAD生物合成。在癌细胞和异种移植肿瘤中，细菌赋予细胞抵抗NAMPT抑制剂的能力，NAMPT是酰胺化NAD补救途径中的限速酶。从机理上讲，将烟酰胺转化为烟酸（一种替代脱酰胺基NAD补救途径的前体）的微生物烟碱酰胺酶（PncA）对于这种保护作用是必要且充分的。使用稳定同位素示踪和微生物缺失的小鼠，研究人员证明了这种细菌介导的脱酰胺作用在许多组织中对口服烟酰胺和烟酰胺核糖苷补充的NAD增强至关重要。总的来说，这些发现揭示了细菌活化的脱酰胺途径在宿主NAD代谢中的重要作用。

据介绍，烟酰胺腺嘌呤二核苷酸（NAD）是所有细胞内数百种代谢反应的辅助因子，在代谢、DNA修复和衰老中起着至关重要的作用。然而，尚不清楚NAD代谢是如何受到环境影响。

附：英文原文

Title: Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway

Author: Igor Shats, Jason G. Williams, Juan Liu, Mikhail V. Makarov, Xiaoyue Wu, Fred B. Lih, Leesa J. Deterding, Chaemin Lim, Xiaojiang Xu, Thomas A. Randall, Ethan Lee, Wenling Li, Wei Fan, Jian-Liang Li, Marina Sokolsky, Alexander V. Kabanov, Leping Li, Marie E. Migaud, Jason W. Locasale, Xiaoling Li

Issue&Volume: 2020/03/03

Abstract: Nicotinamide adenine dinucleotide (NAD), a cofactor for hundreds of metabolic reactionsin all cell types, plays an essential role in metabolism, DNA repair, and aging. However,how NAD metabolism is impacted by the environment remains unclear. Here, we reportan unexpected trans-kingdom cooperation between bacteria and mammalian cells whereinbacteria contribute to host NAD biosynthesis. Bacteria confer resistance to inhibitorsof NAMPT, the rate-limiting enzyme in the amidated NAD salvage pathway, in cancercells and xenograft tumors. Mechanistically, a microbial nicotinamidase (PncA) thatconverts nicotinamide to nicotinic acid, a precursor in the alternative deamidatedNAD salvage pathway, is necessary and sufficient for this protective effect. Usingstable isotope tracing and microbiota-depleted mice, we demonstrate that this bacteria-mediateddeamidation contributes substantially to the NAD-boosting effect of oral nicotinamideand nicotinamide riboside supplementation in several tissues. Collectively, our findingsreveal an important role of bacteria-enabled deamidated pathway in host NAD metabolism.

DOI: 10.1016/j.cmet.2020.02.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30059-0