基于比较基因组学的Clostridium kluyveri己酸代谢途径关键酶生物信息学分析

对3?株白酒来源重要的己酸生产菌株Clostridium kluyveri（NBRC 12016、JZZ和DSM 555）全基因组信息进行比较基因组学分析，聚焦于己酸代谢途径核心催化酶，发现NBRC 12016的己酸代谢途径未得到有效注释，JZZ的己酸代谢途径核心催化酶酰基辅酶A脱氢酶存在注释错误。进一步对C. kluyveri模式菌株DSM 555己酸代谢途径的关键酶硫解酶ThlA进行生物信息学分析，发现DSM 555携带3 拷贝的ThlA，且具有序列多态性，可能与催化脂肪酸代谢链延长的底物特异性相关。结构分析和分子对接表明，硫解酶ThlA1的底物催化属于氧化还原开关调控机制，并预测了酶的关键催化位点和具体的催化过程。上述分析结果有助于为后续进一步改进菌株的己酸生产性能和更好地应用于白酒酿造提供依据。

Bioinformatics Analysis of the Key Enzymes of the Hexanoic Acid Metabolic Pathway in Clostridium kluyveri Based on Comparative Genomics

In this study, the genomic information of three Clostridium kluyveri strains (NBRC 12016, JZZ and DSM 555) were analyzed by comparative genomics with focus on the core enzymes of the hexanoic acid metabolism pathway. It was found that the metabolic pathway of hexanoic acid in NBRC 12016 was not annotated in details and there was mis-annotated information on the core enzyme of the hexanoic acid metabolic pathway in JZZ, acyl coenzyme A dehydrogenase. Bioinformatic analysis was carried out for the key enzyme thiolase (ThlA) of hexanoic acid metabolism in DSM 555. Also, we found that DSM 555 carried three copies of the ThlA gene with sequence polymorphism, which might be related to the substrate specificity of fatty acid chain elongation enzymes. The structural analysis and molecular docking indicated that the catalytic characteristics of ThlA1 contributed to the redox-switch regulatory mechanism. The key catalytic sites and the catalytic process were predicted. The above analysis will be helpful for further improving the hexanoic acid-producing ability of C. kluyveri for application in the brewing of Baijiu.