In silico-guided metabolic engineering of Bacillus subtilis for efficient biosynthesis of purine nucleosides by blocking the key backflow nodes.

ABSTRACT:

Background

Purine nucleosides play essential roles in cellular physiological processes and have a wide range of applications in the fields of antitumor/antiviral drugs and food. However, microbial overproduction of purine nucleosides by de novo metabolic engineering remains a great challenge due to their strict and complex regulatory machinery involved in biosynthetic pathways.

Results

In this study, we designed an in silico-guided strategy for overproducing purine nucleosides based on a genome-scale metabolic network model in Bacillus subtilis. The metabolic flux was analyzed to predict two key backflow nodes, Drm (purine nucleotides toward PPP) and YwjH (PPP-EMP), to resolve the competitive relationship between biomass and purine nucleotide synthesis. In terms of the purin

SUBMITTER: Deng A 

PROVIDER: S-EPMC9367096 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature