Metabolic and genetic factors affecting the productivity of pyrimidine nucleoside in Bacillus subtilis. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Zhu, Hui; Yang, Shao-Mei; Yuan, Zhao-Min; Ban, Rui
• Is Part Of: Microbial cell factories. Volume 14:Issue 1(2015)
• Page Start: 1
• Page End: 12
• Publication Date: 2015-12
• Subjects: Bacillus subtilis -- Cytidine -- Uridine -- Gene deletion -- Gene expression -- Pyrimidine nucleotide biosynthesis; Microbial biotechnology -- Periodicals; Recombinant proteins -- Synthesis -- Periodicals; 660.62
• DOI: 10.1186/s12934-015-0237-1
• Languages: English
• ISSNs: 1475-2859

Abstract

Abstract Background Cytidine and uridine are produced commercially byBacillus subtilis. The production strains of cytidine and uridine were both derivatives from mutagenesis. However, the exact metabolic and genetic factors affecting the productivity remain unknown. Genetic engineering may be a promising approach to identify and confirm these factors. Results With the deletion of thecdd andhom genes, and the deregulation of thepyr operon inBacillus subtilis 168, the engineered strain produced 200.9 mg/L cytidine, 14.9 mg/L uridine and 960.1 mg/L uracil. Then, the overexpressedprs gene led to a dramatic increase of uridine by 25.9 times along with a modest increase of cytidine. Furthermore, the overexpressedpyrG gene improved the production of cytidine, uridine and uracil by 259.5%, 11.2% and 68.8%, respectively. Moreover, the overexpression of thepyrH gene increasesd the yield of cytidine by 40%, along with a modest augments of uridine and uracil. Lastly, the deletion of thenupC-pdp gene resulted in a doubled production of uridine up to 1684.6 mg/L, a 14.4% increase of cytidine to 1423 mg/L, and a 99% decrease of uracil to only 14.2 mg/L. Conclusions The deregulation of thepyr operon and the overexpression of theprs, pyrG andpyrH genes all contribute to the accumulation of pyrimidine nucleoside compounds in the medium. Among these factors, the overexpression of thepyrG andpyrH genes can particularly facilitate the production of cytidine. Meanwhile, the deletion of thenupC-pdp gene can obviously reduce the production of uracil and simultaneously improve the production of uridine.