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II型聚酮酶（PKS） 以从聚酮化合物制备可变但限定长度的聚酮化合物链， 特定的启动器单元和一定数量的扩展器单元。 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， 亚基或通过位点特异性 酮还原酶（KR）和CYC亚基。 其他环化酶和其他 可能需要进行修饰以产生 线性芳香族化合物的类别，其中一些已经证明 医学意义 然而，目前还不知道是否角 芳香族聚酮化合物的组装原理与 描述了产生线性芳族聚酮化合物的PKS。 基因 角型聚酮化合物，包括一个环化酶基因 用于折叠聚酮化合物链以产生角形聚酮化合物 中间体已被克隆并在宿主菌株S. lividans和S.灰绿色的 我们现在正在 表征了在这些宿主中产生的几种聚酮中间体 菌株，以进一步定义PKS、Cnd KR的迭代函数 在生成角形芳香族聚酮中间体中的应用。