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Cloning,expression and characterization of gene sgcD involved in the biosynthesis of novel antitumor lidamycin

Cloning, expression and characterization of gene sgcD involved in the biosynthesis of novel antitumor lidamycin
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摘要 Lidamycin with high antitumor activity is a novel enediyne antitumor antibiotic produced by Streptomyces globisporus C1027. The 75 kb biosynthesis gene cluster of lidamycin containing 33 open reading frames has been cloned from S. globisporus C1027. In this paper, the function of sgcD (ORF24) is investigated. Gene disruption experiment proved that sgcD is involved in lidamy- cin biosynthesis. With homologous comparing analysis, we deduce that sgcD codes aminomutase catalyzing a-tyrosine to b-tyrosine which is one motif for lidamycin. To identify the function of en- zyme coded by sgcD, sgcD is cloned into vector pET30a for inducing expression and the activity of expression product is analyzed. The result showed that the expression product of sgcD has the activity of aminomutase. Aminomutase coded by sgcD is the first characterized enzyme involved in the biosynthesis of enediyne antitumor antibiotics. Our research will be helpful to clarifying the biosynthesis mechanism of such kind of antibiotic and to producing new antitumor compounds. Lidamycin with high antitumor activity is a novel enediyne antitumor antibiotic produced by Streptomyces globisporus C1027. The 75 kb biosynthesis gene cluster of lidamycin containing 33 open reading frames has been cloned from S. globisporus C1027. In this paper, the function of sgcD (ORF24) is investigated. Gene disruption experiment proved that sgcD is involved in lidamy- cin biosynthesis. With homologous comparing analysis, we deduce that sgcD codes aminomutase catalyzing a-tyrosine to b-tyrosine which is one motif for lidamycin. To identify the function of en- zyme coded by sgcD, sgcD is cloned into vector pET30a for inducing expression and the activity of expression product is analyzed. The result showed that the expression product of sgcD has the activity of aminomutase. Aminomutase coded by sgcD is the first characterized enzyme involved in the biosynthesis of enediyne antitumor antibiotics. Our research will be helpful to clarifying the biosynthesis mechanism of such kind of antibiotic and to producing new antitumor compounds.
出处 《Science China(Life Sciences)》 SCIE CAS 2003年第3期310-319,共10页 中国科学(生命科学英文版)
基金 supported by the National Natural Science Foundation of China(Grant No.39870029).
关键词 Streptomyces lidamycin biosynthesis gene disruption aminomutase. Streptomyces, lidamycin, biosynthesis, gene disruption, aminomutase.
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参考文献9

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