title: Metabolic engineering of Bacillus subtilis for biosynthesis of heparosan using heparosan synthase from Pasteurella multocida, PmHS1.
abstract: Heparosan, the capsular polysaccharide discovered in many pathogenic bacteria, is a promising material for heparin preparation. In this study, the Pasteurella multocida heparosan synthase 1 (PmHS1) module was used to synthesize heparosan with controlled molecular weight, while tuaD/gtaB module or gcaD module was responsible for UDP-precursors production in Bacillus subtilis 168. After metabolic pathway optimization, the yield of heparosan was as high as 237.6 mg/L in strain containing PmHS1 module and tuaD/gtaB module, which indicated that these two modules were key factors in heparosan production. The molecular weight of heparosan varied from 39 to 53 kDa, which indicated that heparosan molecular weight could be adjusted by the amount of PmHS1 and the ratio of two UDP precursors. The results showed that it would be possible to produce safe heparosan with appropriate molecular weight which is useful in heparin production.
authors.affiliation: Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Tang
authors.affiliation: Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. wbyao@cpu.edu.cn.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Yao
authors.affiliation: Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. xdgao@cpu.edu.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gao
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D016695:Glycosyltransferases / Q000096:biosynthesis / Q000235:genetics; D060847:Metabolic Engineering; D016979:Pasteurella multocida / Q000201:enzymology / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D016695:Glycosyltransferases; C450833:heparosan synthase
keywords: Heparosan; Metabolic engineering; Molecular weight control; Recombinant Bacillus subtilis