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

• Published in: Bioscience, Biotechnology, and Biochemistry
• Main Authors: Mo, Jian, Ye, Jiang, Chen, Haozhe, Hou, Bingbing, Wu, Haizhen, Zhang, Huizhan
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press (OUP) 2019
• Subjects: Organic Chemistry; Molecular Biology; Applied Microbiology and Biotechnology; General Medicine; Biochemistry; Analytical Chemistry; Biotechnology; Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1080/09168451.2019.1638755; http://academic.oup.com/bbb/article-pdf/83/11/2082/36834786/bbb2082.pdf

ABSTRACT 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.