Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Bioengineering, Tianjin University of Science and Technology, Tianjin, 300457, People's Republic of China.
Industrial Microbiology Laboratory, College of Biotechnology, Tianjin University of Science and Technology, Tianjin Economic and Technological Development Zone, No. 29, 13 Main Street, Tianjin, 300457, People's Republic of China.
Appl Microbiol Biotechnol. 2017 Oct;101(20):7589-7602. doi: 10.1007/s00253-017-8465-4. Epub 2017 Sep 11.
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.
菲奇霉素是一种肽类抗生素，对草酸青霉和金黄色葡萄球菌具有很强的体外活性，甚至对大多数临床使用的抗生素有耐药性的菌株也有活性。从链霉菌属菲奇氏菌中克隆并测序了负责菲奇霉素生物合成的基因簇。它包含 26 个 ORF，位于 30kb 连续 DNA 内。靶向敲除编码基因表明，大多数基因参与了菲奇霉素生物合成的功能部分，如肽组装、调节、抗性和菲奇霉素前体 2-[4-胍基-1-氮杂双环[3.1.0]己烷-2-基]甘氨酸（2-GAHG）的生物合成。在 2-GAHG 合成途径中，硫酸腺苷酰转移酶似乎参与了具有重要药物作用的 1-氮杂双环[3.1.0]己烷环部分的合成，据报道，该部分会导致 DNA 交联或半保留 DNA 复制受损。
