Gene coexpression network analysis reveals a novel metabolic mechanism of Clostridium acetobutylicum responding to phenolic inhibitors from lignocellulosic hydrolysates.
Gene coexpression network analysis reveals a novel metabolic mechanism of Clostridium acetobutylicum responding to phenolic inhibitors from lignocellulosic hydrolysates.
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基因共表达网络分析揭示了丙酮丁醇梭菌响应木质纤维素水解产物酚类抑制剂的新代谢机制
DOI：
10.1186/s13068-020-01802-z
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发表时间：
2020
影响因子：
6.3
通讯作者：
Huang D
中科院分区：
文献类型：
--
作者：
Liu H;Zhang J;Yuan J;Jiang X;Jiang L;Li Z;Yin Z;Du Y;Zhao G;Liu B;Huang D
木质纤维素生物质是一种很有前途的可再生生物化学品和生物燃料资源。然而，木质纤维素水解物（LCH）中存在的抑制剂对丙酮丁醇梭菌（Clostridium acetobutylicum）发酵丙酮丁醇乙醇（ABE）是一个巨大的挑战。特别是，酚类化合物（PC）从LCH严重阻止ABE生产，即使在低浓度。因此，迫切需要深入了解酚类抑制剂引起的细胞内代谢紊乱，并阐明潜在的机制，以确定破坏高效ABE生产的关键工业瓶颈。研究了C.在四种典型的PC（香草醛、香草醛、阿魏酸和对香豆酸）的存在下，分别表征了丙酮丁醇。PC的加入对ABE的产生产生了不同的不可逆影响。具体地，丁香醛显示出对丁醇产生的最大抑制，其次是香草醛、阿魏酸和对香豆酸。随后，基于RNA测序数据的加权基因共表达网络分析（WGCNA）被应用于识别由四个LCH衍生的PC引起的代谢扰动，并提取与胞外发酵性状相关的基因模块。对每个模块中的枢纽基因进行蛋白质-蛋白质相互作用分析和富集分析。结果表明，功能模块是PC依赖的，并共享一些独特的功能。其中对香豆酸引起的转录组干扰最为广泛，特别是影响了核糖体蛋白质的基因表达、鞭毛的组装、DNA的复制、修复和重组，丁香醛引起了核糖体蛋白质的基因表达、淀粉和蔗糖代谢的显著代谢干扰，香草醛主要干扰嘌呤代谢、孢子形成和信号转导，而对苯丙氨酸的干扰主要是对苯丙氨酸的干扰。阿魏酸引起糖基转移酶相关基因表达的代谢紊乱。该研究首次揭示了PC抑制机制的新见解，并为未来的代谢工程工作提供了指导，为开发苯酚耐受菌株奠定了坚实的基础。用于从木质纤维素生物质以高生产率经济上可持续的ABE生产。
Lignocellulosic biomass is a promising resource of renewable biochemicals and biofuels. However, the presence of inhibitors existing in lignocellulosic hydrolysates (LCH) is a great challenge to acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum. In particular, phenolic compounds (PCs) from LCH severely block ABE production even at low concentrations. Thus, it is urgent to gain insight into the intracellular metabolic disturbances caused by phenolic inhibitors and elucidate the underlying mechanisms to identify key industrial bottlenecks that undermine efficient ABE production. In this study, a time-course of ABE fermentation by C. acetobutylicum in the presence of four typical PCs (syringaldehyde, vanillin, ferulic acid, and p-coumaric acid) was characterized, respectively. Addition of PCs caused different irreversible effects on ABE production. Specifically, syringaldehyde showed the greatest inhibition to butanol production, followed by vanillin, ferulic acid, and p-coumaric acid. Subsequently, a weighted gene co-expression network analysis (WGCNA) based on RNA-sequencing data was applied to identify metabolic perturbations caused by four LCH-derived PCs, and extract the gene modules associated with extracellular fermentation traits. The hub genes in each module were subjected to protein–protein interaction analysis and enrichment analysis. The results showed that functional modules were PC-dependent and shared some unique features. Specifically, p-coumaric acid caused the most extensive transcriptomic disturbances, particularly affecting the gene expressions of ribosome proteins and the assembly of flagella, DNA replication, repair, and recombination; the addition of syringaldehyde caused significant metabolic disturbances on the gene expressions of ribosome proteins, starch and sucrose metabolism; vanillin mainly disturbed purine metabolism, sporulation and signal transduction; and ferulic acid caused a metabolic disturbance on glycosyl transferase-related gene expressions. This study uncovers novel insights into the inhibitory mechanisms of PCs for the first time and provides guidance for future metabolic engineering efforts, which establishes a powerful foundation for the development of phenol-tolerant strains of C. acetobutylicum for economically sustainable ABE production with high productivity from lignocellulosic biomass.
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影响因子：
3
作者：
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影响因子：
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