Genome Combination Improvement Strategy Promotes Efficient\nSpinosyn Biosynthesis in Saccharopolyspora spinosa

Spinosyns are secondary\nmetabolites produced by Saccharopolyspora spinosa known for their potent\ninsecticidal properties and broad pesticidal spectrum. We report significant\nadvancements in spinosyn biosynthesis achieved through a genome combination\nimprovement strategy in S. spinosa.\nBy integrating modified genome shuffling with ultraviolet mutation\nand multiomics analysis, we developed a high-yield spinosyn strain\ndesignated as YX2. The levels of most proteins and metabolites linked\nto primary metabolism and spinosyn biosynthesis were greater in this\nstrain than those in S. spinosa. Based\non these insights, we overexpressed 15 relevant functional genes to\nenhance the conversion of fatty acids into acetyl-coenzyme A. Notably,\nthe overexpression of <i>acd</i> (YX2_3432) significantly\nincreased the spinosyn yield, reaching 1120 ± 108 mg/L, which\nis about 12 times higher than that produced by S. spinosa. This study presents a valuable and straightforward strategy that\ncan be broadly applied to enhance the production of secondary metabolites\nin actinomycetes.