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

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...

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Bibliographic Details
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
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Summary: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.

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