烟酰胺腺嘌呤二核苷酸
生物合成
化学
酶
天然产物
烟酰胺
辅因子
生物化学
NAD+激酶
生物
作者
Lena Barra,Takayoshi Awakawa,Kohei Shirai,Zhongliang Hu,Ghader Bashiri,Ikuro Abe
出处
期刊:Nature
[Springer Nature]
日期:2021-12-08
卷期号:600 (7890): 754-758
被引量:30
标识
DOI:10.1038/s41586-021-04214-7
摘要
β-Nicotinamide adenine dinucleotide (β-NAD) is a pivotal metabolite for all living organisms and functions as a diffusible electron acceptor and carrier in the catabolic arms of metabolism1,2. Furthermore, β-NAD is involved in diverse epigenetic, immunological and stress-associated processes, where it is known to be sacrificially utilized as an ADP-ribosyl donor for protein and DNA modifications, or the generation of cell-signalling molecules3,4. Here we report the function of β-NAD in secondary metabolite biosynthetic pathways, in which the nicotinamide dinucleotide framework is heavily decorated and serves as a building block for the assembly of a novel class of natural products. The gatekeeping enzyme of the discovered pathway (SbzP) catalyses a pyridoxal phosphate-dependent [3+2]-annulation reaction between β-NAD and S-adenosylmethionine, generating a 6-azatetrahydroindane scaffold. Members of this novel family of β-NAD-tailoring enzymes are widely distributed in the bacterial kingdom and are encoded in diverse biosynthetic gene clusters. The findings of this work set the stage for the discovery and exploitation of β-NAD-derived natural products.
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