FUNCTIONAL BIOSYNTHETIC ROLES OF POLYKETIDE SYNTHASES, CYCLASES & KETOREDUCTASES

聚酮化合物合成酶、环化酶的生物合成功能

• 批准号: 6309115
• 负责人: CHARLES R HUTCHINSON
• 金额: $ 0.75万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6309115
• 关键词: bacteria; bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource; biotechnology; enzymes; nuclear magnetic resonance spectroscopy

Iterative type II polyketide synthases (PKSs) have been determined to produce polyketide chains of variable but defined length from a specific starter unit and a certain number of extender units. They also specify the initial regiospecific folding and cyclization pattern of nascent polyketides either through the action of a cyclase (CYC) subunit or through the combined influence of site-specific ketoreductase (KR) and CYC subunits. Additional cyclases and other modifiactions may be necessary to yield the various known members of the class of linear aromatic compoinds, several of which have proven medical significance. However, it was not known whether angular aromatic polyketides would assemble using the same principles as described for PKSs that yield linear aromatic polyketides. Genes for angular polyketides including a cyclase gene thought to be responsible for folding of the polyketide chain to produce angular polyketide intermediates have been cloned and expressed in host strains S. lividans and S. glaucescens. We are now in the process of characterizing several polyketide intermediates produced in these host strains to further define the iterative functions of the PKSs, Cnd KRs in generating angular aromatic polyketide intermediates.

已经确定了迭代的II型聚酮合成酶(PKS) 从一种具有可变但固定长度的聚酮链 特定起动器单元和一定数量的延伸器单元。他们 还指定了初始区域特异性折叠和环化模式 通过环化酶(CyC)的作用 子单元或通过站点特定的组合影响 酮还原酶(KR)和CyC亚基。其他周期酶和其他 可能需要进行修改以生成各种已知成员 一类线性芳香化合物，其中几个已经证明 医学上的意义。然而，目前还不知道是否有棱角 芳香族聚酮将使用相同的原理进行组装 描述了产生线性芳香族聚酮的PKSS。基因 含有环化酶基因的角状多酮被认为是 用于折叠聚酮链以产生有角度的聚酮 中间体已被克隆并在宿主菌S. 青枯草和白蜡虫。我们现在正在进行 在这些宿主中产生的几种聚酮中间体的特征 菌株以进一步定义PKSS、CND KRS的迭代函数 在生成有角度的芳香族聚酮中间体方面。