Effects of sirtuins on the riboflavin production in Ashbya gossypii
Effects of sirtuins on the riboflavin production in Ashbya gossypii
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DOI：
10.1007/s00253-021-11595-2
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发表时间：
2021-09-24
影响因子：
5
通讯作者：
Park, Enoch Y.
中科院分区：
文献类型：
--
作者：
Kato, Tatsuya;Azegami, Junya;Park, Enoch Y.
本研究的重点是sirtuins，催化NAD（+）依赖的蛋白脱乙酰酶的反应，在A。棉。烟酰胺是一种已知的沉默调节蛋白抑制剂，它使A.棉蚜菌落在5mM时呈现较深的黄色。为了研究sirtuins在A. gossypii中核黄素合成中的作用，我们将其基因组中的4个sirtuin基因（AgHST 1，AgHST 2，AgHST 3，AgHST 4）进行了破坏。棉。获得了AgHST 1、AgHST 3和AgHST 4的增量菌株，但没有获得AgHST 2的增量菌株。AgHST 1增量和AgHST 3增量菌株产生的核黄素量比WT菌株高约4.3倍和2.9倍。AgHST 3增量菌株显示出比WT菌株更低的人沉默调节蛋白6（SIRT6）样活性，并且仅在AgHST 3增量菌株中观察到比WT菌株更高量的组蛋白H3 K9和K56（H3K9ac和H3K56ac）的乙酰化。这些结果表明，AgHst 3是A.并对A. gossypii的核黄素合成产生影响。棉。在5 mM羟基脲和50 μ M喜树碱的存在下，其引起DNA损伤，特别是双链DNA断裂，WT菌株菌落的颜色变成更深的黄色。此外，尽管没有检测到显著差异，但羟基脲显著导致产生高约1.5倍量的核黄素，并且喜树碱也增强核黄素产生。喜树碱有增加H3K56ac表达的趋势，但羟基脲处理不能增加H3K56ac的表达。本研究表明AgHst 1和AgHst 3参与了A.分别通过NAD代谢和H3的乙酰化作用对棉蚜进行调控。这一新的发现是澄清sirtuins在A.关键点烟酰胺促进了棉阿舒囊霉的核黄素合成，AgHST1或AgHST3基因的缺失也促进了核黄素的合成，H3K56的乙酰化也促进了核黄素的合成。
This study focuses on sirtuins, which catalyze the reaction of NAD(+)-dependent protein deacetylase, for riboflavin production in A. gossypii. Nicotinamide, a known inhibitor of sirtuin, made the color of A. gossypii colonies appear a deeper yellow at 5 mM. A. gossypii has 4 sirtuin genes (AgHST1, AgHST2, AgHST3, AgHST4) and these were disrupted to investigate the role of sirtuins in riboflavin production in A. gossypii. AgHST1 increment , AgHST3 increment , and AgHST4 increment strains were obtained, but AgHST2 increment was not. The AgHST1 increment and AgHST3 increment strains produced approximately 4.3- and 2.9-fold higher amounts of riboflavin than the WT strain. The AgHST3 increment strain showed a lower human sirtuin 6 (SIRT6)-like activity than the WT strain and only in the AgHST3 increment strain was a higher amount of acetylation of histone H3 K9 and K56 (H3K9ac and H3K56ac) observed compared to the WT strain. These results indicate that AgHst3 is SIRT6-like sirtuin in A. gossypii and the activity has an influence on the riboflavin production in A. gossypii. In the presence of 5 mM hydroxyurea and 50 mu M camptothecin, which causes DNA damage, especially double-strand DNA breaks, the color of the WT strain colonies turned a deeper yellow. Additionally, hydroxyurea significantly led to the production of approximately 1.5 higher amounts of riboflavin and camptothecin also enhanced the riboflavin production even through the significant difference was not detected. Camptothecin tended to increase the amount of H3K56ac, but the amount of H3K56ac was not increased by hydroxyurea treatment. This study revealed that AgHst1 and AgHst3 are involved in the riboflavin production in A. gossypii through NAD metabolism and the acetylation of H3, respectively. This new finding is a step toward clarifying the role of sirtuins in riboflavin over-production by A. gossypii.Key pointsNicotinamide enhanced the riboflavin production in Ashbya gossypii.Disruption of AgHST1 or AgHST3 gene also enhanced the riboflavin production in Ashbya gossypii.Acetylation of H3K56 led to the enhancement of the riboflavin production in Ashbya gossypii.