Liamocins, as the secondary metabolites synthesized and secreted by Aureobasidium spp., consist of a single mannitol or a single arabitol head group partially O-acylated with three 3,5-dihydroxydecanoic ester groups or directly esterified with three or four 3,5-dihydroxydecanoic ester tails. Very recently, the whole synthetic pathway of liamocins in A. melanogenum 6-1-2 has been elucidated. It was found that the promoter sequences of all the genes related to liamocin synthesis in A. melanogenum 6-1-2 had stress regulatory elements with core sequences of AGGGG or CCCCT. Therefore, expression of all the genes would be regulated by the Msn2. In this study, it was found that removal of the single one MSN2 gene in A. melanogenum 6-1-2 made the mutant decrease yield of extracellular liamocin by 92.28 %, while complementation of the MSN2 gene in the mutant rendered liamocin synthesis to be restored. When A. melanogenum 6-1-2 was cultured in the liamocin fermentation medium with high glucose and low nitrogen, the Msn2 was localized in the nucleus and positively regulated the expression of the genes related to liamocin biosynthesis. Furthermore, when the key BCY1 gene encoding regulatory subunit of the cAMP-PKA signaling pathway in A. melanogenum 6-1-2 was knocked out, the amount of extracellular liamocins synthesized by the mutant was decreased by 96.73 % and the Msn2 was localized in the cytoplasm. Similarly, when the key HOG1 gene in the HOG1 signaling pathway was deleted, liamocin biosynthesis in the knockout strain was decreased by 98.09 %. However, it was found that the Hog1 may be one part of the general transcription complex to regulate the transcription of the MSN2 gene, leading to the reduced Msn2 and liamocin synthesis in the mutant. In addition, the key TOR1 gene and SNF1 gene in the TOR1 signaling pathway and the SNF1 signaling pathway were not involved in the regulation of the Msn2 activity and liamocin synthesis. It was concluded that the transcriptional activator Msn2, the HOG1 signaling pathway and the cAMP-PKA signaling pathway were involved in the regulation of liamocin biosynthesis and production.

中文翻译：

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cAMP-PKA 和 HOG1 信号通路通过转录激活因子 Msn2 在 Aureobasidium melanogenum 中通过不同方式调节 liamocin 的产生

Liamocins 作为由 Aureobasidium spp. 合成和分泌的次级代谢物，由单个甘露醇或单个阿拉伯糖醇头部基团组成，该头部基团被三个 3,5-二羟基癸酸酯基团部分 O-酰化或直接被三个或四个 3,5-二羟基癸酸酯化酯尾。最近，已经阐明了 A. melanogenum 6-1-2 中 liamocins 的整个合成途径。发现A. melanogenum 6-1-2中所有与liamocin合成相关的基因的启动子序列均具有核心序列为AGGGG或CCCCT的胁迫调控元件。因此，所有基因的表达均受Msn2调控。本研究发现，去除A. melanogenum 6-1-2中的单个MSN2基因使细胞外liamocin的突变体产量降低92.28%，而突变体中 MSN2 基因的互补使 liamocin 合成得以恢复。当A. melanogenum 6-1-2在高糖低氮的liamocin发酵培养基中培养时，Msn2定位于细胞核内，并正向调控liamocin生物合成相关基因的表达。此外，当 A. melanogenum 6-1-2 中编码 cAMP-PKA 信号通路调节亚基的关键 BCY1 基因被敲除后，该突变体合成的胞外 liamocins 量减少了 96.73%，Msn2 定位于细胞质。同样，当 HOG1 信号通路中的关键 HOG1 基因被删除时，敲除菌株中的 liamocin 生物合成减少了 98.09%。然而，发现Hog1可能是调节MSN2基因转录的通用转录复合物的一部分，导致突变体中Msn2和liamocin合成减少。此外，TOR1信号通路和SNF1信号通路中的关键TOR1基因和SNF1基因均不参与Msn2活性和利莫霉素合成的调控。结论是转录激活因子 Msn2、HOG1 信号通路和 cAMP-PKA 信号通路参与了 liamocin 生物合成和生产的调控。