A complete nicotinate degradation pathway in the microbial eukaryote Aspergillus nidulans.

A complete nicotinate degradation pathway in the microbial eukaryote Aspergillus nidulans.
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DOI:
10.1038/s42003-022-03684-3
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发表时间:
2022-07-21
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
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--
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在细菌中存在几种截然不同的烟酸分解的需氧和厌氧途径。在这里,通过反向遗传学和分析技术,我们阐明了构巢曲霉,一个完整的真核生物烟酸利用途径。这种真菌和其他子囊菌中存在的途径与细菌的途径完全不同。鉴别了所有中间代谢产物。同源蛋白质,编码的11个基因(hxn)映射在三个集群是由一个特定的转录因子的共同调控。几个酶促步骤没有原核等价物,两种代谢产物,3-羟基哌啶-2,6-二酮和5,6-二羟基哌啶-2-酮,以前在任何生物体中都没有鉴定出,后者是一种新的化合物。水解开环产生α-羟基戊二酸,这是一种在类似的原核途径中未检测到的化合物。我们早期的Hxn蛋白的系统发育分析与此完整的生化途径一起说明真菌和细菌之间的分解代谢途径的趋同进化。在构巢曲霉中描述了一种新的烟酸降解途径,并鉴定了以前在原核物种中未发现的代谢产物。这是第一个在真核生物中描述的这种途径。
Several strikingly different aerobic and anaerobic pathways of nicotinate breakdown are extant in bacteria. Here, through reverse genetics and analytical techniques we elucidated in Aspergillus nidulans, a complete eukaryotic nicotinate utilization pathway. The pathway extant in this fungus and other ascomycetes, is quite different from bacterial ones. All intermediate metabolites were identified. The cognate proteins, encoded by eleven genes (hxn) mapping in three clusters are co-regulated by a specific transcription factor. Several enzymatic steps have no prokaryotic equivalent and two metabolites, 3-hydroxypiperidine-2,6-dione and 5,6-dihydroxypiperidine-2-one, have not been identified previously in any organism, the latter being a novel chemical compound. Hydrolytic ring opening results in α-hydroxyglutaramate, a compound not detected in analogous prokaryotic pathways. Our earlier phylogenetic analysis of Hxn proteins together with this complete biochemical pathway illustrates convergent evolution of catabolic pathways between fungi and bacteria. A novel nicotinate degradation pathway is described in Aspergillus nidulans, with metabolic products identified that were not previously found in prokaryotic species. This is the first such pathway to be described in a eukaryote.
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