Mechanistic Insight for Improving Butenyl-spinosyn Production Through Combined ARTP/UV Mutagenesis and Ribosome Engineering in
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Butenyl-spinosyn is a highly effective, wide-spectrum and environmentally-friendly biological insecticide produced by . However, its scale-up is impeded due to its lower titer in wild-type strains. In this work, ARTP/UV mutagenesis and ribosome engineering were employed to enhance the butenyl-spinosyn production, and a stable mutant aG6 with high butenyl-spinosyn yield was successfully obtained. For the first time, the fermentation results in the 5 L bioreactor demonstrated that the butenyl-spinosyn produced by mutant aG6 reached the maximum value of 130 mg/L, almost 4-fold increase over the wild-type strain WT. Furthermore, comparative genomic, transcriptome and target metabolomic analysis revealed that the accumulation of butenyl-spinosyn was promoted by alterations in ribosomal proteins, branched-chain amino acid degradation and oxidative phosphorylation. Conclusively, the proposed model of ribosome engineering combined with ARTP/UV showed the improved biosynthesis regulation of butenyl-spinosyn in .
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