Identification of specific genes related to efficient Monensin biosynthesis in Streptomyces cinnamonensis with genomic analysis

Abstract

Monensin, a polyether ionophore antibiotic that is produced by Streptomyces cinnamonensis through fermentation, is extensively utilized in both agricultural and pharmaceutical sectors. This study focused on identifying some specific genes and critical metabolic pathways related to the monensin biosynthesis in S. cinnamonensis for efficient monensin production with a genome analysis. Results show that genes of the strain were significantly enriched in the monensin synthetic pathway, including primary metabolic (central carbon and fatty acids) processes, energy metabolism, and secondary metabolite biosynthesis, which was largely potential in the supply of sufficient building precursors and energy. The annotated specific genes were predominantly located in metabolic pathways and secondary metabolites biosynthesis, accounting for 90.63% and 39.06%, respectively. Among them, specific genes, fadD, fadE, fadB, and fadA in the fatty acid degradation pathway were apparently the most prominent. With single overexpression, these genes resulted in the strain increasing monensin titer by 14%, 11%, 22%, and 10%, respectively. Further, with the tandem overexpression, an engineered strain M5 was successfully constructed. The strain was capable of producing 18.88 g/L of monensin at 288 h at shake-flask level and 37.31 g/L via fed-batch in a 50-L bioreactor, which is 1.3 folds and 1.2 folds, respectively, that of the starting strain. To our knowledge, this represents the highest level reported to date, which is of a big industrial promise. This study provides a genetic foundation for elucidating the monensin synthesis mechanism and paves the way for metabolic engineering modifications and industrial production.

Keywords

Antibiotic fermentation / Comparative genomics / Metabolic engineering / Monensin / Overexpression

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Funding

National Natural Science Foundation of China(21776114)

National First-class Discipline Program of Light Industry Technology and Engineering(QGJC20230203)

111 Project(111-2-06)

Postgraduate Research and Practice Innovation Program of Jiangsu Province(KYCX22-2377)

RIGHTS & PERMISSIONS

Jiangnan University