Center for Systems Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Genetic Engineering and Bioinformatics Program, Graduate School, Kasetsart University, Bangkok 10900, Thailand.
Cells. 2020 Feb 10;9(2):401. doi: 10.3390/cells9020401.
Beyond comparative genomics, we identified 85 sugar transporter genes in , clustering into nine subfamilies as sequence- and phylogenetic-based functional classification, presuming the versatile capability of the fungal growths on a range of sugars. Further analysis of the global gene expression patterns of showed 123 genes were significantly expressed across the sucrose, glucose, and xylose cultures. The sugar transporters specific for pentose were then identified by gene-set enrichment analysis. Of them, the putative pentose transporter, CCM_06358 gene, was highest expressed in the xylose culture, and its functional role in xylose transport was discovered by the analysis of conserved structural motifs. In addition, a battery of molecular modeling methods, including homology modeling, transport pathway analysis, residue interaction network combined with molecular mechanics Poisson-Boltzmann surface area simulation (MM-PBSA), was implemented for probing the structure and function of the selected pentose transporter (CCM_06358) as a representative of sugar transportome in . Considering the network bottlenecks and structural organizations, we further identified key amino acids (Phe38 and Trp441) and their interactions with other residues, contributing the xylose transport function, as verified by binding free energy calculation. The strategy used herein generated remarkably valuable biological information, which is applicable for the study of sugar transportome and the structure engineering of targeted transporter proteins that might link to the production of bioactive compounds derived from xylose metabolism, such as cordycepin.
除了比较基因组学，我们还在中鉴定了 85 个糖转运蛋白基因，根据序列和系统发育将其聚类为九个亚家族，推测真菌在一系列糖上生长的多功能性。对的全局基因表达模式的进一步分析表明，123 个基因在蔗糖、葡萄糖和木糖培养物中均有显著表达。然后通过基因集富集分析鉴定了特定戊糖的糖转运蛋白。其中，推测的戊糖转运蛋白 CCM_06358 基因在木糖培养物中表达最高，其在木糖转运中的功能作用通过保守结构模体分析得到了发现。此外，采用了一系列分子建模方法，包括同源建模、运输途径分析、残基相互作用网络与分子力学泊松-玻尔兹曼表面面积模拟（MM-PBSA）相结合，用于探测所选戊糖转运蛋白（CCM_06358）的结构和功能作为糖转运组在中的代表。考虑到网络瓶颈和结构组织，我们进一步鉴定了关键氨基酸（Phe38 和 Trp441）及其与其他残基的相互作用，这些氨基酸有助于木糖转运功能，如结合自由能计算所验证的。本文所采用的策略生成了非常有价值的生物学信息，可应用于糖转运组学的研究和靶向转运蛋白的结构工程，这些可能与木糖代谢衍生的生物活性化合物（如虫草素）的生产有关。
