Studies On The Thermostability Of Methanogens Based On Metabolic Network

Because thermophiles have strong adaptability to high temperature, they have greatapplication value in genetic engineering, protein engineering, fermentation engineering andutilizationof mineral resources in recent years. In order to clarify heat-resistant mechanism ofthese thermophiles from system level and guide further applications of thermophiles inindustry, this paper focuses on the research of the metabolic network of methanogens. Westudied the metabolic network’s topology structure and modular, and explored the differenceof metabolic network of heat resistance between mesophilic methanogen Methanosarcinaacetivorans (M. acetivorans) and thermophilic methanogen Methan opyrus kandleri(M. kandleri).The paper firstly reconstructed the metabolic network of mesophilic methanogen M.acetivorans and thermophilic methanogen M. kandleri based on the KEGG database, thenverified the metabolic networks which had characters such as small world and scale-freenetworks.According to global comparison of metabolic networks, the pathways00010(glycolysis/glucose dysplasia),00020(citric acid cycle) and00250(Alanine, aspartate andglutamate metabolism) are important pathways in mesophilic methanogen M. acetivorans andthermophilic methanogen M. kandleri. Their degrees are the highest of the entire networkwhich mean that they are appeared in early stage of the evolution. Meanwhile, the relationbetween the classification of the enzymes of metabolic network and degree was examinedbased on the global metabolic network. The lowest degree is synthetases and the higest degreeis oxidoreductases. And transferases are found in their metabolic networks. In order tocompare and analyze the relation between topology and heat resistance of their metabolicnetworks, the degree, degree centrality, closeness centrality, betweenness centrality, clusteringcoefficient and diameter of their metabolic network were calculated. The clusteringcoefficients of the mesophilic methanogen M. acetivorans and thermophilic methanogenM. kandleri metabolic network are much higher than random network of the same size andtopology. It indicates that the two species have high modular structure. And the metabolicnetwork of mesophilic methanogen M. acetivorans has longer average path length, largerdiameter than thermophilic methanogen M. kandleri. It shows that the overall structure ofmesophilic methanogen M. acetivorans is relative low density and loose network structure.The highly closeness subnetwork can reflect the network’s global characteristics, so it isan important factor in comparing the metabolic network of different species of large-scalenetwork. Our experiments shows that the9-core has27enzymes of the mesophilicmethanogen M. acetivorans and7-core of the thermophilic methanogen M. kandleri has19enzymes. The7-core of the thermophic methanogen M. kandleri is divided into two smallnetworks. One has shared enzymes of the two methanogens, the other has particular enzymesof the7-core of thermophilic methanogen M. kandleri. These unique enzymes are associatedwith the synthesis of tyrosine, so the heat resistance of thermophilic methanogen M. kandlerimay be affected by the intracellular tyrosine. The metabolic networks are similar to other complex network systems. They havemodular structure. The effective recognition and extracting the function module of metabolicnetworks can help us grasping the implied function information. Therefore, based on theglobal research of metabolic network, Girvan and Newman’s module identification algorithm(GN) and simulated annealing algorithm (SA) were adopted for analysis the functionalsignificance of these characteristics at the system level. The metabolic network of themesophilic methanogen M. acetivorans is composed of39modules. And the metabolicnetwork of the M. kandleri is divided into30modules. The hub modules are1,4,15and16ofM. acetivorans because the connections of these modular nodes are much closer thanother modules. The hub modules are module1and11of the thermophilic methanogenM. kandleri. The certain functional meaning network modules are identified using GNalgorithm. There are four modules belonging to carbohydrates, one module belonging to thebiosynthesis of secondary metabolism of M. acetivorans. And two modules belong to thecarbohydrate metabolism of the thermophilic methanogen M. kandleri.Biological network alignment is an important research method to the study of organism’sstructure, function and evolutionary analysis. Finally, global metabolic networks of the twomethanogens and hub module were compared after using MI-GRAAL algorithm. All specificenzymes of hub modules K-1and K-11of thermophilic methanogen M. kandleri are includedin a highly close k-core subnetwork. So the comparative study on the metabolic network ofdifferent species can use respectively highly closest subnetwork, modular, and networkalignment methods, etc.