The putative methyltransferase LaeA regulates mycelium growth and cellulase production in Myceliophthora thermophila.
The putative methyltransferase LaeA regulates mycelium growth and cellulase production in Myceliophthora thermophila.
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DOI：
10.1186/s13068-023-02313-3
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发表时间：
2023-04-03
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--
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具有利用复杂碳源能力的丝状真菌已被开发为生物化学品生产的平台。嗜热毁丝霉已被开发为生产木质纤维素分解酶和植物生物质基生物燃料和生物化学品的生物炼制中的细胞工厂。然而，真菌生长速度慢、纤维素利用率低是影响目标产物产量和生产率的重要因素，需要我们进一步探索和改进。在这项研究中，我们全面探讨了推定的甲基转移酶LaeA在调节菌丝生长，糖消耗和纤维素酶表达的作用。嗜热毁丝霉（Myceliophthora thermophila）中laeA基因的缺失显著促进了菌丝生长和葡萄糖消耗。对LaeA调控网络的进一步研究表明，在该菌中，多种生长调节因子Cre-1、Grf-1、Grf-2和Grf-3作为碳代谢的负阻遏物受到LaeA的调控。我们还确定了磷酸烯醇式丙酮酸羧激酶（PCK）是与真菌营养生长相关的代谢网络的核心节点，其增强部分有助于突变体ΔlaeA的糖消耗和真菌生长的增加。值得注意的是，LaeA参与调节纤维素酶基因及其转录调控因子的表达。与野生型菌株相比，ΔlaeA的胞外蛋白和内切葡聚糖酶活性峰值分别提高了30.6%和5.5%。此外，全局组蛋白甲基化测定表明LaeA与调节H3 K9甲基化水平相关。LaeA在调节真菌生理上的正常功能依赖于甲基转移酶活性。本研究阐明了LaeA在调节真菌生长和纤维素酶产生中的功能并阐明了其调节网络，这将大大加深我们对LaeA在丝状真菌中调节机制的认识，并为通过代谢工程改善工业真菌菌株的发酵特性提供新的策略。在线版本包含补充材料，可通过10.1186/s13068-023-02313-3获得。
Filamentous fungi with the ability to use complex carbon sources has been developed as platforms for biochemicals production. Myceliophthora thermophila has been developed as the cell factory to produce lignocellulolytic enzymes and plant biomass-based biofuels and biochemicals in biorefinery. However, low fungal growth rate and cellulose utilization efficiency are significant barriers to the satisfactory yield and productivity of target products, which needs our further exploration and improvement. In this study, we comprehensively explored the roles of the putative methyltransferase LaeA in regulating mycelium growth, sugar consumption, and cellulases expression. Deletion of laeA in thermophile fungus Myceliophthora thermophila enhanced mycelium growth and glucose consumption significantly. Further exploration of LaeA regulatory network indicated that multiple growth regulatory factors (GRF) Cre-1, Grf-1, Grf-2, and Grf-3, which act as negative repressors of carbon metabolism, were regulated by LaeA in this fungus. We also determined that phosphoenolpyruvate carboxykinase (PCK) is the core node of the metabolic network related to fungal vegetative growth, of which enhancement partially contributed to the elevated sugar consumption and fungal growth of mutant ΔlaeA. Noteworthily, LaeA participated in regulating the expression of cellulase genes and their transcription regulator. ΔlaeA exhibited 30.6% and 5.5% increases in the peak values of extracellular protein and endo-glucanase activity, respectively, as compared to the WT strain. Furthermore, the global histone methylation assays indicated that LaeA is associated with modulating H3K9 methylation levels. The normal function of LaeA on regulating fungal physiology is dependent on methyltransferase activity. The research presented in this study clarified the function and elucidated the regulatory network of LaeA in the regulation of fungal growth and cellulase production, which will significantly deepen our understanding about the regulation mechanism of LaeA in filamentous fungi and provides the new strategy for improvement the fermentation properties of industrial fungal strain by metabolic engineering. The online version contains supplementary material available at 10.1186/s13068-023-02313-3.
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影响因子：
5.2
作者：
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