文献类型：期刊文献

英文题名：Mn2+ modulates the production of mycophenolic acid in Penicillium brevicompactum NRRL864 via reactive oxygen species signaling and the investigation of pb-pho

作者：Chen, Mianhui[1];Shen, Yaling[1];Lin, Lin[2,3];Wei, Wei[1];Wei, Dongzhi[1]

机构：[1]East China Univ Sci & Technol, Newworld Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China;[3]Natl Engn Res Ctr Nanotechnol, Res Lab Funct Nanomat, Shanghai 200241, Peoples R China

年份：2022

卷号：126

期号：6-7

起止页码：461

外文期刊名：FUNGAL BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001137789600007)】；

基金：This work is supported by the grant from the National Key Research and Development Program of China (2021YFC2100300). M.C. andW.W. received funding from the Shanghai Natural Science Foundation (No. 20ZR1415400), the Shanghai outstanding technical leaders plan 19XD1431900, 19XD1431800, the National Natural Science Foundation of China (Grant No. 81830052, 81530053), and Shanghai Key Laboratory of Molecular Imaging (18DZ2260400).

语种：英文

外文关键词：Manganese-calcium-ROS; Penicillium brevicompactum; Cell wall integrity; Mycophenolic acid; Heat shock

摘要：Although Penicillium brevicompactum is a widely used commercial strain for the manufacture of mycophenolic acid, there are few findings of Ca2+, Mn2+, and reactive oxygen species (ROS) interaction. Metal ions play a crucial role in physiological metabolism. Calcium, as the important second messenger, influences fungus growth, virulence, and stress responses. The concentration of cytosolic Ca2+ was influenced by the Mn2+, which demonstrated the crosstalk between calcium and manganese. In the previous study, the crosstalk between calcium and ROS has been discovered and verified, which modified the secondary metabolism and enhanced the yield of MPA (Mycophenolic Acid). A higher concentration of Mn2+ in the fermentation broth causes an increase in cytoplasmic Ca2+ and ROS (Reactive Oxygen Species), enhancing the yield of MPA by about 20 % higher and disclosing the cascade regulation with the Mn2+, Ca2+, and ROS. To be more specific, the intracellular concentration of ROS at 6 mM Mn2+ is about 1.5 times higher than that at 0.6 mM. Furthermore, we identify an Mn2+ transport protein, designated as Pb-PHO, which shows 71.2 % identity to the inorganic phosphate transporter PHO84 (Q0CBJ6) from Aspergillus terreus. At the same time, the Delta Pb-pho exhibits damage to the cell wall integrity, while the OE-pho displays a more normal phenotype at high osmotic stress. The high-affinity Ca2+ channel, Pb-CCH, is examined via knockdown to demonstrate the crosstalk between Mn2+ and Ca2+. The results show that the addition of Mn2+ remits the negative influence of pb-cch knockdown and the addition of Ca2+ remits the negative influence of pb-pho knockdown, demonstrating the relationship between cytoplasmic Mn2+ and Ca2+. Taken together, our results demonstrate the mechanism of a manganeseinduced cascade of manganese-calcium-ROS and reveal a signal pathway-relative method to illustrate the manganese-induced increase of MPA production in Penicillium brevicompactum. Furthermore, we discover and identify an Mn2+ transport protein, PbePHO, which is subcellular localized at the plasma membrane and proved to affect the cell wall integrity. (c) 2022 British Mycological Society. Published by Elsevier Ltd. All rights reserved.