Comparative transcriptome analysis reveals the underlying mechanism for over-accumulation of menaquinone-7 in Bacillus subtilis natto mutant

Abstract This study combined whole-genome sequencing, compound mutagenesis, and comparative transcriptome analysis methods to investigate the menaquinone-7 (MK-7) metabolism and regulation in Bacillus subtilis natto. Whole genome sequencing identified that the wild-type MK-7 producing strain BN0 contains one single circular chromosome in size of 4,119,230 bp, harboring 4603 protein-coding genes, and two plasmids in size of 64,309 and 5820 bp respectively. In addition, UV-ARTP (Ultraviolet -atmospheric and room temperature plasm) compound mutagenesis was performed in BN0, resulting in 50.6% improvement of MK-7 production in the mutant BN19-A. Further comparative transcriptome analysis revealed that: (1) the key genes (e.g glpA, dxs, ispF and ispH) involved in the glycerol metabolism pathway and MEP pathway were significantly up-regulated; (2) most genes related to the formation of spore were down-regulated; and (3) many genes (e.g tatA, bmr and bcr) involved in Tat secretion pathway, ABC transporters and MFS transporters were up-regulated. These results help us get insights into the underlying metabolic mechanism of MK-7 production in B. subtilis natto, and provide more potential molecular targets to be engineered for further strain improvement.