Mechanisms of Enhanced Natamycin Biosynthesis in Streptomyces gilvosporeus 717: An Integrated Genomic and Transcriptomic Analysis
Abstract
Abstract Natamycin is a polyene macrolide antifungal compound produced by Streptomyces species and is widely used in food preservation and antifungal therapy. Random mutagenesis is proved an effective strategy for improving natamycin production, but the genetic and transcriptional basis underlying high-yield phenotypes remains incompletely understood. In this study, we generated a high-producing mutant, Streptomyces gilvosporeus 717, from its parental strain 712 by atmospheric and room-temperature plasma (ARTP) mutagenesis and integrated whole-genome resequencing (WGS) with time-resolved transcriptome sequencing (RNA-seq) to investigate the mechanisms associated with enhanced natamycin biosynthesis. In 15 L fed-batch fermentation, strain 717 produced 21.15 g/L natamycin at 168 h, representing a 74.2% increase over strain 712. WGS identified 320 high-confidence variants in strain 717, including 241 SNPs and 79 InDels. Most variants were located in non-coding, intergenic, or upstream regulatory regions (298/320, 93.1%), whereas only 22 variants (6.9%) were located in coding sequences or were annotated as functionally relevant coding-region variants. RNA-seq at 72 h and 120 h revealed extensive stage-dependent transcriptional reprogramming, with 817 and 2097 differentially expressed genes (DEGs), respectively. The early response was characterized by upregulation of ABC transporter components, including ATP-binding proteins and permeases, whereas the later response involved…
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