Polyketide synthase gene coupled to the peptide synthetase module involved in the biosynthesis of the cyclic heptapeptide microcystin

Polyketide synthase gene coupled to the peptide synthetase module involved in the biosynthesis of the cyclic heptapeptide microcystin
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DOI:
10.1093/oxfordjournals.jbchem.a022670
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发表时间:
2000-05-01
影响因子:
2.7
通讯作者:
Shirai, M
Shirai, M
中科院分区:
生物学4区
文献类型:
--
作者:
Nishizawa, T;Ueda, A;Shirai, M

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肽合成酶基因操纵子由 mcyA、mcyB、抗 mcyC 组成,已被鉴定用于激活和掺入微囊藻毒素的五种氨基酸成分 [T.西泽等人。 (1999) J.生物化学。 126、52-529]。通过对产生微囊藻毒素的铜绿微囊藻 K-139 的另外 34 kb DNA 进行测序,我们鉴定了残留的微囊藻毒素合成酶基因操纵子,其由 mcyD、mcyE、mcyF 和 mcyG 组成,方向与 mcyABC 操纵子相反。 McyD由两个聚酮合酶模块组成,McyE在N端包含一个聚酮合酶模块,在C端包含一个肽合成酶模块。发现McyF与氨基酸消旋酶相似,McyG由N端的肽合成酶模块和C端的聚酮化合物合酶组成。微囊藻毒素合成酶基因簇在另一种产生微囊藻毒素的菌株Microcystis sp, S-70中保守,该菌株产生微囊藻毒素-LR、-RR和-YR。微囊藻属 S-70 中 mcyA、mcyD 或 mcyE 的插入诱变消除了微囊藻毒素的产生。总之,mcyDEFG 操纵子被认为负责 3-氨基-9-甲氧基-2,6,8-三甲基-10-苯基十-4,6-二烯酸 (Adda) 生物合成,以及将 Adda 和谷氨酸掺入微囊藻毒素分子中。
The peptide synthetase gene operon, which consists of mcyA, mcyB, anti mcyC, for the activation and incorporation of the five amino acid constituents of microcystin has been identified [T. Nishizawa et al. (1999) J. Biochem. 126, 52-529]. By sequencing an additional 34 kb of DNA from microcystin-producing Microcystis aeruginosa K-139, we identified the residual microcystin synthetase gene operon, which consists of mcyD, mcyE, mcyF,and mcyG, in the opposite orientation to the mcyABC operon. McyD consisted of two polyketide synthase modules, and McyE contained a polyketide synthase module at the N-terminus and a peptide synthetase module at the C-terminus. McyF was found to exhibit similarity to amino acid racemase, McyG consisted of a peptide synthetase module at the N-terminus and a polyketide synthase at the C-terminus, The microcystin synthetase gene cluster was conserved in another microcystin-producing strain, Microcystis sp, S-70, which produces Microcystin-LR, -RR, and -YR. Insertional mutagenesis of mcyA, mcyD, or mcyE in Microcystis sp, S-70 abolished microcystin production. In conclusion, the mcyDEFG operon is presumed to be responsible for 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda) biosynthesis, and the incorporation of Adda and glutamic acid into the microcystin molecule.