PMID- 32050592 OWN - NLM STAT- MEDLINE DCOM- 20210210 LR - 20210210 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 9 IP - 2 DP - 2020 Feb 10 TI - Probing Carbon Utilization of Cordyceps militaris by Sugar Transportome and Protein Structural Analysis. LID - 10.3390/cells9020401 [doi] LID - 401 AB - Beyond comparative genomics, we identified 85 sugar transporter genes in Cordyceps militaris, 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 C. militaris 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 C. militaris. 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. FAU - Sirithep, Kanokwadee AU - Sirithep K AD - Center for Systems Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China. AD - Genetic Engineering and Bioinformatics Program, Graduate School, Kasetsart University, Bangkok 10900, Thailand. FAU - Xiao, Fei AU - Xiao F AD - Center for Systems Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China. FAU - Raethong, Nachon AU - Raethong N AD - Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand. FAU - Zhang, Yuhan AU - Zhang Y AD - Center for Systems Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China. FAU - Laoteng, Kobkul AU - Laoteng K AD - Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand. FAU - Hu, Guang AU - Hu G AD - Center for Systems Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China. FAU - Vongsangnak, Wanwipa AU - Vongsangnak W AD - Center for Systems Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China. AD - Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand. AD - Omics Center for Agriculture, Bioresources, Food, and Health, Faculty of Science, Kasetsart University (OmiKU), Bangkok 10900, Thailand. LA - eng GR - RSA6180001/Thailand Research Fund/International GR - -/Kasetsart University/International GR - 31872723/National Natural Science Foundation of China/International GR - -/Thailand Graduate Institute of Science and Technology/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200210 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Fungal Proteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Sugars) RN - 7440-44-0 (Carbon) RN - A1TA934AKO (Xylose) SB - IM MH - Amino Acid Motifs MH - Amino Acid Sequence MH - Biological Transport MH - Carbon/*metabolism MH - Cordyceps/genetics/*metabolism MH - Fungal Proteins/*chemistry/*metabolism MH - Gene Regulatory Networks MH - Membrane Transport Proteins/metabolism MH - *Metabolome MH - Phylogeny MH - Sugars/*metabolism MH - Thermodynamics MH - Transcriptome/genetics MH - Xylose/metabolism PMC - PMC7072658 OTO - NOTNLM OT - carbon metabolism OT - comparative genomics OT - cordyceps militaris OT - network analysis OT - protein structure OT - sugar transporter COIS- The authors declare that they have no conflicts of interest EDAT- 2020/02/14 06:00 MHDA- 2021/02/11 06:00 PMCR- 2020/02/01 CRDT- 2020/02/14 06:00 PHST- 2019/12/04 00:00 [received] PHST- 2020/01/24 00:00 [revised] PHST- 2020/02/05 00:00 [accepted] PHST- 2020/02/14 06:00 [entrez] PHST- 2020/02/14 06:00 [pubmed] PHST- 2021/02/11 06:00 [medline] PHST- 2020/02/01 00:00 [pmc-release] AID - cells9020401 [pii] AID - cells-09-00401 [pii] AID - 10.3390/cells9020401 [doi] PST - epublish SO - Cells. 2020 Feb 10;9(2):401. doi: 10.3390/cells9020401.