title: In silico metabolic engineering of Bacillus subtilis for improved production of riboflavin, Egl-237, (R,R)-2,3-butanediol and isobutanol.
abstract: Bacillus subtilis is a Gram-positive sporiferous bacterium widely used in a variety of industrial fields as a producer of high-quality vitamins, enzymes and proteins. Many genetic modifications and evolutionary engineering optimisations aiming at obtaining a better performing strain for its products have been studied. As genome-scale metabolic network models have gained significant popularity as effective tools in metabolic phenotype studies, we reconstructed a genome-scale metabolic network of B. subtilis-iBsu1147. The accuracy of iBsu1147 is validated by growth on various carbon sources, single gene knockout and large fragment non-essential gene knockout simulations. The model is used for the in silico metabolic engineering design of reactions over/underexpressed or knockout for increasing the production of four important products of B. subtilis: riboflavin, cellulase Egl-237, (R,R)-2,3-butanediol and isobutanol. The simulation predicted candidate reactions related to the improvement of strain performance on related products. The prediction is partly supported by previously published results. Due to the complexity of the biological system, it is difficult to manually find the factors that are not directly related to the production of the target compounds. The in silico predictions provide more choices for further strain improvement for these products.
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Hao
authors.forename: Binbin
authors.initials: B
authors.lastname: Han
authors.forename: Hongwu
authors.initials: H
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Bincai
authors.initials: B
authors.lastname: Tang
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Xueming
authors.initials: X
authors.lastname: Zhao
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D000440:Butanols / Q000378:metabolism*; D002072:Butylene Glycols / Q000378:metabolism*; D002480:Cellulase / Q000096:biosynthesis* / Q000235:genetics; D003198:Computer Simulation; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D012256:Riboflavin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D000440:Butanols; D002072:Butylene Glycols; C026978:2,3-butylene glycol; C040507:isobutyl alcohol; D002480:Cellulase; C421179:Egl-237 protein, Bacillus; D012256:Riboflavin