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.

迭代 II 型聚酮合酶 (PKS) 已确定 生产可变但确定长度的聚酮化合物链 特定的启动单元和一定数量的扩展单元。 他们 还指定初始区域特异性折叠和环化模式 通过环化酶（CYC）的作用形成新生聚酮化合物 亚基或通过位点特异性的综合影响 酮还原酶 (KR) 和 CYC 亚基。 额外的环化酶和其他 可能需要进行修改才能产生各种已知的成员 线性芳香族化合物类别，其中一些已被证明 医学意义。 但尚不知道是否有角度 芳香族聚酮化合物的组装原理与 描述了产生线性芳香族聚酮化合物的 PKS。 基因 有角聚酮化合物，包括被认为负责的环化酶基因 用于折叠聚酮化合物链以产生有角聚酮化合物 中间体已在宿主菌株 S 中克隆并表达。 变青石和青青石榴。 我们现在正在处理 表征在这些宿主中产生的几种聚酮化合物中间体 菌株进一步定义 PKS、Cnd KR 的迭代函数 用于生成角芳香族聚酮化合物中间体。