title: N-methylphenylalanyl-dehydrobutyrine diketopiperazine, an A-factor mimic that restores antibiotic biosynthesis and morphogenesis in Streptomyces globisporus 1912-B2 and Streptomyces griseus 1439.
abstract: The cell-free extracts of a landomycin E-producing strain, Streptomyces globisporus 1912-2, were shown to contain a low-molecular-weight compound that, like A-factor, restored the landomycin E and streptomycin biosynthesis and sporulation of the defective mutants S. globisporus 1912-B2 and S. griseus 1439, respectively. The compound was purified by thin layer chromatography and HPLC. It had an absorption maximum at λmax=245 nm and a molecular mass of m/z 244. On the basis of NMR spectroscopy ((1)H, (13)C, HSQC, HMBC, COSY and NOE) the chemical structure of the compound was elucidated as 6-benzyl-3-eth-(Z)-ylidene-1-methyl-piperazine-2,6-dione ((L)-N-methylphenylalanyl-dehydrobutyrine diketopiperazine (MDD)). The sequences of arpA genes in S. globisporus 1912-2 and S. griseus NBRC 13350 are highly conserved. An explanation for the observed biological activity of MDD was proposed.
authors.affiliation: Department of Genetics of Microorganisms, D.K. Zabolotny Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Matselyukh
authors.affiliation: Department of Chemistry, Institute for Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mohammadipanah
authors.affiliation: Department of Chemistry, Institute for Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Laatsch
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, USA.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rohr
authors.affiliation: Sector of Screening of Natural Compounds, G.F. Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Efremenkova
authors.affiliation: Department of Organic Chemistry, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Khilya
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001483:Base Sequence; D002457:Cell Extracts; D002474:Cell-Free System; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D054659:Diketopiperazines / Q000737:chemistry / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009024:Morphogenesis; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D013305:Streptomyces griseus / Q000235:genetics / Q000378:metabolism*; D013307:Streptomycin / Q000096:biosynthesis*
chemical_list: C000596371:6-benzyl-3-ethylidene-1-methylpiperazine-2,6-dione; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002457:Cell Extracts; D054659:Diketopiperazines; D010456:Peptides, Cyclic; C113593:landomycin E; D013307:Streptomycin