Genome shuffling of Streptomyces gilvosporeus for improving natamycin production.

Improvement of natamycin production by Streptomyces gilvosporeus ATCC 13326 was performed by recursive protoplast fusion in a genome-shuffling format. After four rounds of genome shuffling, the best producer, GS 4-21, with genetic stability was obtained and its production of natamycin reached 4.69 ± 0.05 g/L in shaking flask after 96 h cultivation, which was increased by 97.1% and 379% in comparison with the highest parental strain pop-72A(r)07 and the initial strain ATCC 13326, respectively. Compared with the initial strain ATCC 13326, the recombinant GS 4-21 presented higher polymorphism. Fifty-four proteins showed differential expression levels between the recombinant GS 4-21 and initial strain ATCC 13326. Of these proteins, 34 proteins were upregulated and 20 proteins were downregulated. Of the upregulated proteins, one protein, glucokinase regulatory protein, was involved in natamycin biosynthesis. This comprehensive analysis would provide useful information for understanding the natamycin metabolic pathway in S. gilvosporeus.