Mechanistic studies of PHB biosynthesis

PHB生物合成机理研究

• 批准号: 7670444
• 负责人: Ping Li
• 金额: $ 2.67万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670444
• 关键词: 3-hydroxybutyryl-coenzyme A; Active Sites; Anabolism; Bacteria; Binding; Carbon; Catalysis; Characteristics; Chemicals; Coenzyme A; Crystal Formation; Crystallization; Cysteine; Elastomers; Engineering; Environment; Enzymes; Goals; Heart Valves; Methods; Modeling; Phase; Plastics; Polyesters; Polymerase; Polymers; Property; Radiolabeled; Regulation; Scheme; Series; Structure; Techniques; Tissue Engineering; Work; analog; base; beta-Hydroxybutyrate; design; inhibitor/antagonist; interest; microbial; monomer; mutant; polymerization; radiotracer; scaffold; thioester

DESCRIPTION (provided by applicant): Polyhydroxyalkanoates (PHAs) are a class of microbial polyesters produced by many bacteria as intracellular carbon and energy storage polymers. They display material properties ranging from thermoplastics to elastomers. An important characteristic of PHAs is their inherent biodegradability in various environments or biosystems. Thus, the desire to replace the conventional petrochemical-based plastics with biodegradable plastics in an environmentally friendly and economically competitive fashion has served an impetus for this project. The new engineered materials are expected find wide applications such as in heart valves and as scaffolds for tissue engineering. The long-term goal of this proposal is to identify and understand the machinery involved in PHA biosynthesis and its regulation. Specifically, in order to distinguish between the two elongation mechanisms proposed for the formation of polyhydroxybutyrates (PHBs), approaches involving chemical methods, in combination with the construction of mutant enzymes, to trap the polymerization intermediates will be employed. Crystal structures will greatly enhance the understanding of the elongation mechanism and help design mechanism-based inhibitors more rationally. However, to date, no crystals of PHB synthases have been obtained although some progress has been made. A series of compounds will be prepared and explored as covalent inhibitors of synthases in an effort to obtain their crystals along with mutagenetic methods. PHAs are of general interest as they possess properties that range from thermoplastics to elastomers and are biodegradable. Understanding the PHA biosynthesis is crucial to engineering new materials that are currently being examined for their applications such as in heart valves and as scaffolds for tissue engineering. The goal of this project is to identify and understand the machinary involved in PHA biosynthesis and its regulation.

描述（由申请人提供）：聚羟基链烷酸酯（PHA）是一类由许多细菌产生的微生物聚酯，作为细胞内碳和储能聚合物。它们具有从热塑性塑料到弹性体的各种材料特性。 PHA 的一个重要特性是其在各种环境或生物系统中固有的生物降解性。因此，以环保且具有经济竞争力的方式用可生物降解塑料取代传统石化塑料的愿望推动了该项目。新的工程材料预计会得到广泛的应用，例如心脏瓣膜和组织工程支架。该提案的长期目标是识别和了解 PHA 生物合成及其调控所涉及的机制。具体来说，为了区分形成聚羟基丁酸酯（PHB）的两种延伸机制，将采用涉及化学方法的方法，结合突变酶的构建，以捕获聚合中间体。晶体结构将极大地增强对延伸机制的理解，并有助于更合理地设计基于机制的抑制剂。然而，迄今为止，虽然取得了一些进展，但尚未获得PHB合酶的晶体。将制备和探索一系列化合物作为合成酶的共价抑制剂，以期通过诱变方法获得它们的晶体。 PHA 受到普遍关注，因为它们具有从热塑性塑料到弹性体的各种特性，并且可生物降解。了解 PHA 生物合成对于工程新材料至关重要，目前正在检查其应用，例如心脏瓣膜和组织工程支架。该项目的目标是识别和了解 PHA 生物合成及其调控所涉及的机制。