Multi-omics profiling reveals the molecular mechanism of Bifidobacterium animalis BB04 in co-culture with Wickerhamomyces anomalus Y-5 to induce bifidocin A synthesis

Abstract

Bacteriocin is a kind of natural substance that can effectively inhibit bacteria, but its production usually limited by environment. Co-culture is a strategy to stimulate bacteriocin production. Bifidocin A produced by Bifidobacterium animalis BB04, is a novel bacteriocin with a broad-spectrum antimicrobial active of foodborne bacteria. In order to enhance bifidocin A production, bacteriocin-inducing strains were screened firstly in co-cultivation. Then, the molecular mechanism of co-cultural induction was investigated by transcriptomic and proteomic analysis. Finally, the key inducing metabolites were identified by using targeted metabolomic technology. The results showed that Wickerhamomyces anomalus Y-5 in co-cultivation could significantly enhance bifidocin A production with 3-fold increase compared with mono-culture. The induction may not depend on direct contact with cells, but on continuous stimulation of inducing substances in a certain concentration. In co-cultivation, W. anomalus Y-5 up-regulated Hxk2 and Tap42 to activate glucose-cAMP and Tor and HOG-MAPK pathway, stimulated the expression of the retrograde gene, produced glutamine and glycerol to maintain activity. During this process, glutamine, inosine, guanosine, adenine, uracil, fumaric acid and pyruvic acid produced by W. anomalus Y-5 could induce the synthesis of bifidocin A. In conclusion, W. anomalus Y-5 in co-cultivation induced the synthesis of bifidocin A by regulating various signaling pathways to produce inducing substances. These findings lay a foundation for bifidocin A high-efficient synthesis and provide a new perspectives on the industrial production of bacteriocin.