title: Mutational biosynthesis of neomycin analogs by a mutant of neomycin-producing Streptomyces fradiae.
abstract: Neomycin, produced by Streptomyces fradiae, has been widely used for the treatment of bacterial infections in clinical and agricultural applications. In this study, a neomycin nonproducing mutant of S. fradiae was obtained by gene disruption technique for mutational biosynthesis. A crucial gene neoC (neo7) which encodes 2-deoxystreptamine (2-DOS) synthases was disrupted. The mutant could resume producing neomycin in the presence of 2-DOS. Salen derivatives of 2-DOS were synthesized and individually added to cultures of the mutant. Antibacterial activity of the mutasynthesis products against Staphylococcus aureus and four plant pathogenic bacteria (Pseudomonas solanacarum, Erwinia carotovora, Xanthomonas oryzae, and Xanthomonas campestris) was detected quantitatively by Oxford cup method. It is suggested that all 2-DOS derivatives were incorporated by the mutant into new active neomycin analogs except for 2-DOS derivative 2d ((1R,2r,3S,4R,6S)-4,6-bis((E)-3,5-di-tert-butyl-2-hydroxybenzylideneamino)cyclohexane-1,2,3-triol). Neomycin analogs produced by feeding 2-DOS derivative 2a ((1R,2r,3S,4R,6S)-4,6-bis((E)-2 hydroxybenzylideneamino)cyclohexane-1,2,3-triol) to cultures of the mutant displayed a similar antibacterial activity with neomycin produced by wild strain.
authors.affiliation: Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, Sichuan University, Chengdu, Sichuan 610064, People's Republic of China.
authors.forename: Guanying
authors.initials: G
authors.lastname: Shi
authors.forename: Xingang
authors.initials: X
authors.lastname: Zhang
authors.forename: Lang
authors.initials: L
authors.lastname: Wu
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
authors.forename: Ke
authors.initials: K
authors.lastname: Tao
authors.forename: Taiping
authors.initials: T
authors.lastname: Hou
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D009154:Mutation; D009355:Neomycin / Q000031:analogs & derivatives / Q000096:biosynthesis*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009355:Neomycin
references.citation: Antimicrob Agents Chemother. 2002 May;46(5):1546-9
references.pmid: 11959595
references.citation: Org Biomol Chem. 2005 Apr 21;3(8):1410-8
references.pmid: 15827636
references.citation: J Antimicrob Chemother. 1984 Jan;13 Suppl A:9-22
references.pmid: 6365884
references.citation: J Bacteriol. 1948 Feb;55(2):235-40
references.pmid: 16561452
references.citation: Biochem Biophys Res Commun. 2001 Oct 5;287(4):870-4
references.pmid: 11573945
references.citation: Science. 1949 Mar 25;109(2830):305-7
references.pmid: 17782716
references.citation: Folia Microbiol (Praha). 2009;54(2):91-6
references.pmid: 19418244
references.citation: J Antibiot (Tokyo). 2004 May;57(5):351-4
references.pmid: 15303497
references.citation: Bioorg Med Chem Lett. 2001 May 7;11(9):1127-31
references.pmid: 11354359
references.citation: Folia Microbiol (Praha). 2009;54(2):97-104
references.pmid: 19418245
references.citation: Folia Microbiol (Praha). 2008;53(5):395-401
references.pmid: 19085073
references.citation: Proc Natl Acad Sci U S A. 1969 May;63(1):198-204
references.pmid: 5257963
references.citation: Nat Prod Rep. 2006 Dec;23(6):864-74
references.pmid: 17119636
references.citation: FEBS Lett. 1999 Feb 19;445(1):73-9
references.pmid: 10069377
references.citation: Science. 1992 Aug 21;257(5073):1064-73
references.pmid: 1509257
references.citation: J Antibiot (Tokyo). 1974 Dec;27(12):917-21
references.pmid: 4468277
references.citation: Curr Microbiol. 2003 Sep;47(3):237-43
references.pmid: 14570276
references.citation: Mol Cells. 2005 Aug 31;20(1):90-6
references.pmid: 16258246
references.citation: Biochemistry. 2001 Dec 25;40(51):15612-23
references.pmid: 11747436
references.citation: EMBO J. 2000 Jan 4;19(1):1-9
references.pmid: 10619838
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9791-5
references.pmid: 9707554