Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis
Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis
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DOI：
10.1126/science.284.5418.1368
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发表时间：
1999-05-21
期刊：
影响因子：
56.9
通讯作者：
Hutchinson, CR
中科院分区：
文献类型：
--
作者：
Kennedy, J;Auclair, K;Hutchinson, CR
聚酮是微生物中普遍存在的次级代谢产物，其生产过程类似于脂肪酸生物合成，可以在特定的生物合成步骤中抑制还原或脱水反应，从而产生一系列通常在医学上有用的产品。洛伐他汀生物合成簇包含两个I型聚酮合成酶基因。主要的非阿克肽衍生骨架的合成被发现需要先前已知的迭代洛伐他汀非阿克肽合成酶（LNKS）。加上至少一个与LNKS相互作用的额外蛋白（LovC），这是正确处理生长的聚酮链和生产二氢莫纳可林l所必需的。非重复洛伐他汀二酮合成酶（LDKS）酶指定2-甲基丁酸盐的形成，并与另一个负责从该聚酮和莫纳可林J组装洛伐他汀的转移酶（LovD）密切相互作用。
Polyketides, the ubiquitous products of secondary metabolism in microorganisms, are made by a process resembling fatty acid biosynthesis that allows the suppression of reduction or dehydration reactions at specific biosynthetic steps, giving rise to a wide range of often medically useful products. The Lovastatin biosynthesis cluster contains two type I polyketide synthase genes. Synthesis of the main nonaketide-derived skeleton was found to require the previously known iterative Lovastatin nonaketide synthase (LNKS), plus at least one additional protein (LovC) that interacts with LNKS and is necessary for the correct processing of the growing polyketide chain and production of dihydromonacolin L. The noniterative lovastatin diketide synthase (LDKS) enzyme specifies formation of 2-methylbutyrate and interacts closely with an additional transesterase (LovD) responsible for assembling Lovastatin from this polyketide and monacolin J.