Identification and characterization of the ficellomycin biosynthesis gene cluster from Streptomyces ficellus

• Published in: Applied microbiology and biotechnology Vol. 101; no. 20; pp. 7589 - 7602
• Main Authors: Liu, Yang, Li, Meng, Mu, Huiyan, Song, Shuting, Zhang, Ying, Chen, Kun, He, Xihong, Wang, Haikuan, Dai, Yujie, Lu, Fuping, Yan, Zhongli, Zhang, Huitu
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2017; Springer Nature B.V
• Subjects: Anti-Infective Agents - metabolism; Antibiotics; Applied Genetics and Molecular Biotechnology; Biomedical and Life Sciences; Biosynthesis; Biosynthetic Pathways - genetics; Biotechnology; Cloning, Molecular; Crosslinking; Deoxyribonucleic acid; DNA; DNA biosynthesis; Gene Knockout Techniques; Gene Targeting; Glycine; Life Sciences; Microbial Genetics and Genomics; Microbiology; Multigene Family; Open Reading Frames; Peptides; Peptides - metabolism; Sequence Analysis, DNA; Streptomyces; Streptomyces - genetics; Streptomyces - metabolism; Sulfate adenylyltransferase; Sulfates; Synthesis; Gene cluster; Ficellomycin; Antibiotics; Aziridine; Streptomyces ficellus
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-017-8465-4

Ficellomycin is a peptide-like antibiotic which exhibits potent in vitro activity against Penicillium oxalicum and Staphylococcus aureus , even against strains resistant to most clinically used antibiotics. The gene cluster responsible for ficellomycin biosynthesis was cloned from Streptomyces ficellus and sequenced. It was found to contain 26 ORFs and is located within 30 kb of contiguous DNA. Targeted disruption of the encoding genes revealed that most were involved in the functional section of ficellomycin biosynthesis, such as peptide assembly, regulation, resistance, and biosynthesis of the precursor of ficellomycin 2-[4-guanidyl-1-azabicyclo[3.1.0]hexan-2-yl] glycine (2-GAHG). Within the 2-GAHG synthesis pathway, a sulfate adenylyltransferase appears to be involved in the synthesis of the pharmaceutically important 1-azabicyclo[3.1.0]hexane ring moiety, which has been reported to cause DNA cross-linking or impairment of semiconservative DNA replication.