Studies on a second and third ring cyclization in anthracycline biosynthesis
Studies on a second and third ring cyclization in anthracycline biosynthesis
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DOI：
10.7164/antibiotics.56.143
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发表时间：
2003-02-01
影响因子：
3.3
通讯作者：
Ylihonko, K
中科院分区：
文献类型：
--
作者：
Hautala, A;Torkkell, S;Ylihonko, K
本文重点研究异源基因表达在蒽环类生物合成中的第二环和第三环环化。首先，用质粒 pSgs44 和 pSYE66 异源互补不产生蒽环类的鲫链霉菌突变体 D2 来产生道诺霉素，质粒 pSgs44 和 pSYE66 分别含有假定的 S. galilaeus 和 S. nogalater 环化酶基因。 D2 的环化酶基因 dpsY 中的点突变已将甘氨酸变为丝氨酸，导致酶失活。其次，来自 S. nogalater 的推定环化酶基因 snoaM 在 S. nogalater 的基因盒中表达。 lividans TK24 和 S. coelicolor CH999 研究环化酶基因对金霉素生产的影响以及内源基因对生产概况的影响。获得的结果证实，闭合聚酮化合物的第二个和第三个环的环化酶在蒽环类生物合成中是必需的。
This paper focuses on study of second and third ring cyclization in anthracycline biosyhthesis by a heterologous gene expression. Firstly, anthracycline non-producing Streptomyces peucetius mutant, D2 was heterologously complemented to produce daunomycins with plasmids pSgs44 and pSYE66, which contain putative cyclase genes of S. galilaeus and S. nogalater, respectively. A point mutation in the cyclase gene dpsY of D2 has changed glycine to serine resulting inactivation of the enzyme. Secondly, the putative cyclase gene snoaM from S. nogalater, was expressed in a gene cassette in,S. lividans TK24 and S. coelicolor CH999 to study the influence of the cyclase gene on auramycinone production and the impact of endogenous genes on production profiles. the results obtained confirms that a cyclase closing the second and third ring of a polyketide is essential in anthracycline biosynthesis.