Mutational biosynthesis of neomycin analogs by a mutant of neomycin-producing Streptomyces fradiae

Mutational biosynthesis of neomycin analogs by a mutant of neomycin-producing Streptomyces fradiae
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产新霉素弗氏链霉菌突变体突变生物合成新霉素类似物

DOI:
10.1007/s12223-011-0082-5
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发表时间:
2011-11
期刊:
Folia Microbiol
影响因子:
--
通讯作者:
陶科
陶科
中科院分区:
其他
文献类型:
--
作者:
史冠莹;侯太平;陶科

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新霉素是由弗兰迪链霉菌产生的,在临床和农业应用中被广泛用于治疗细菌感染。在本研究中,通过基因阻断技术获得了一株不产生新霉素的链球菌产新霉素突变株。编码2-脱氧链胺(2-DOS)合成酶的关键基因neC(Ne7)被破坏。在2-DOS存在下,该突变株可恢复产生新霉素。合成了2-DOS的Salen衍生物,并将其单独添加到突变体的培养物中。用牛津杯法定量检测突变产物对金黄色葡萄球菌和4种植物病原菌(青枯假单胞菌、胡萝卜欧文氏菌、水稻黄单胞菌和野油菜黄单胞菌)的抑菌活性。结果表明,除2-DOS衍生物的2D((1R,2r,3S,4R,6S)-4,6-bis((E)-3,5-di-tert-butyl-2-hydroxybenzylideneamino)cyclohexane-1,2,3-triol).外,所有的2-DOS衍生物都被突变体引入到新的活性新霉素类似物中。将2-DOS衍生物2a((1R,2R,3S,4R,6S)-4,6-bi((E)-2)hydroxybenzylideneamino)cyclohexane-1,2,3-triol)加入到该突变株的培养物中,所产生的新霉素类似物具有与野生菌株产生的新霉素相似的抗菌活性。
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.
新霉素对胡萝卜软腐欧文氏菌亚种的作用机制
DOI: 10.1016/j.pestbp.2009.07.002
发表时间: 2009-10
影响因子: 4.7
作者:
崔文华;侯太平;陶科
通讯作者: 陶科
DOI: 10.1351/pac197749091361
发表时间: 1977
影响因子: 1.8
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K. Rinehart
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DOI: 10.1007/s12223-009-0013-x
发表时间: 2009-05
影响因子: 2.6
作者:
M. Myronovskyy;B. Ostash;I. Ostash;V. Fedorenko
通讯作者: M. Myronovskyy;B. Ostash;I. Ostash;V. Fedorenko
DOI: --
发表时间: 2000
期刊: --
影响因子: --
作者:
T. Kieser
通讯作者: T. Kieser
DOI: 10.1007/s00284-002-3945-9
发表时间: 2003-09-01
影响因子: 2.6
作者:
Mehta, R;Champney, WS
通讯作者: Champney, WS