College of Marine Life Science, Ocean University of China, Yushan Road, No. 5, Qingdao, China.
College of Marine Life Science, Ocean University of China, Yushan Road, No. 5, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, 266003 Qingdao, China.
Int J Biol Macromol. 2020 Aug 15;157:591-603. doi: 10.1016/j.ijbiomac.2020.04.174. Epub 2020 Apr 25.
Pullulan is an important polysaccharide. Although its synthetic pathway in Aureobasidium melanogenum has been elucidated, the mechanism underlying its biosynthesis as regulated by signaling pathway and transcriptional regulator is still unknown. In this study, it was found that the expression of the UGP1 gene encoding UDPG-pyrophosphorylase (Ugp1) and other genes which were involved in pullulan biosynthesis was controlled by the transcriptional activator Msn2 in the nuclei of yeast-like fungal cells. The Ugp1 was a rate-limiting enzyme for pullulan biosynthesis. In addition, the activity and subcellular localization of the Msn2 were regulated only by the cAMP-PKA signaling pathway. When the cAMP-PKA activity was low, the Msn2 was localized in the nuclei, the UGP1 gene was highly expressed, and pullulan was actively synthesized. By contrast, when the cAMP-PKA activity was high, the Msn2 was localized in the cytoplasm and the UGP1 gene expression was disabled so that pullulan was stopped, but lipid biosynthesis was actively enhanced. This study was the first to report that pullulan and lipid biosynthesis in yeast-like fungal cells were regulated by the Msn2 and cAMP-PKA signaling pathway. Elucidating the regulation mechanisms was important to understand their functions and enhance pullulan and lipid biosynthesis.
茁霉多糖是一种重要的多糖。虽然其在出芽短梗霉中的合成途径已经阐明，但信号通路和转录调控因子对其生物合成的调节机制尚不清楚。本研究发现，编码 UDPG-焦磷酸化酶（Ugp1）的 UGP1 基因和其他参与茁霉多糖生物合成的基因的表达受酵母样真菌细胞核中转录激活子 Msn2 的控制。Ugp1 是茁霉多糖生物合成的限速酶。此外，Msn2 的活性和亚细胞定位仅受 cAMP-PKA 信号通路的调节。当 cAMP-PKA 活性较低时，Msn2 定位于细胞核中，UGP1 基因高度表达，茁霉多糖被积极合成。相反，当 cAMP-PKA 活性较高时，Msn2 定位于细胞质中，UGP1 基因表达失活，因此茁霉多糖停止合成，但脂质生物合成被积极增强。本研究首次报道了酵母样真菌细胞中的茁霉多糖和脂质生物合成受 Msn2 和 cAMP-PKA 信号通路的调节。阐明这些调控机制对于理解它们的功能和增强茁霉多糖和脂质的生物合成具有重要意义。
