Cloning and identification of the Frigocyclinone biosynthetic gene cluster from Streptomyces griseus strain NTK 97

• Main Authors: Mo, Jian, Ye, Jiang, Haozhe Chen, Bingbing Hou, Haizhen Wu, Huizhan Zhang
• Format: Text
• Language: unknown
• Published: Taylor & Francis 2019
• Subjects: Biochemistry; Microbiology; FOS Biological sciences; Genetics; Molecular Biology; Immunology; FOS Clinical medicine; 80699 Information Systems not elsewhere classified; FOS Computer and information sciences; Developmental Biology; 110309 Infectious Diseases; FOS Health sciences; Antarc*; Antarctica
• Online Access: https://dx.doi.org/10.6084/m9.figshare.8867867; https://tandf.figshare.com/articles/Cloning_and_identification_of_the_Frigocyclinone_biosynthetic_gene_cluster_from_i_Streptomyces_griseus_i_strain_NTK_97/8867867

Frigocyclinone is a novel antibiotic with antibacterial and anticancer activities. It is produced by both Antarctica-derived Streptomyces griseus NTK 97 and marine sponge-associated Streptomyces sp. M7_15. Here, we first report the biosynthetic gene cluster of frigocyclinone in the S. griseus NTK 97. The frigocyclinone gene cluster spans a DNA region of 33-kb which consists of 30 open reading frames (ORFs), encoding minimal type II polyketide synthase, aromatase and cyclase, redox tailoring enzymes, sugar biosynthesis-related enzymes, C-glycosyltransferase, a resistance protein, and three regulatory proteins. Based on the bioinformatic analysis, a biosynthetic pathway for frigocyclinone was proposed. Second, to verify the cloned gene cluster, CRISPR-Cpf1 mediated gene disruption was conducted. Mutant with the disruption of beta-ketoacyl synthase encoding gene frig20 fully loses the ability of producing frigocyclinone, while inactivating the glycosyltransferase gene frig1 leads to the production of key intermediate of anti-MRSA anthraquinone tetrangomycin. Cloning and identification of the frigocylinone biosynthetic gene cluster provide a deep insight into the biosynthetic pathway and will contribute to development of novel antibiotics via genetic engineering.