SusChEM: Engineering E. coli for improved production of polyhydroxyalkanoate (PHA)-based biodegradable plastics

1263905 - Nomura Polyhydroxyalkanoates（PHA）是微生物生产的生物基和可生物降解的聚合物，具有广泛的用途，从大宗商品产品中不可生物降解的石油基塑料的替代品到生物医学应用。 限制PHA广泛用于更专门应用的因素之一是缺乏对重复单元组成的控制，并且由此不能生产具有所需物理性质的聚合物。 该研究项目的长期目标是对E。用于生产具有所需材料性质的扩展类别的PHA材料。 由3-5个碳原子的重复单元组成的PHA被称为短链长PHA（SCL-PHA），并且倾向于在性质上是热塑性的但缺乏韧性，而由6-14个碳原子的重复单元组成的PHA被称为中链长PHA（MCL-PHA），并且倾向于是弹性体的。 在先前的研究中已经证明，由80- 95%SCL和5- 20%MCL重复单元组成的SCL-MCL PHA共聚物具有与普通石油基塑料非常相似的材料性质。 该项目的目的是进一步开发菌株，使其能够从可再生糖原料中生产具有理想材料特性的SCL-MCL PHA和PHA-共-聚乳酸（PLA）共聚物，并从乳酸和脂肪酸中生产具有特定重复单元组成的新型PHA-共-PLA共聚物。这将通过合成生物学、代谢工程、蛋白质工程和合成化学方法的组合来实现，以改善PHA的生产。这些研究的成功完成将导致新的聚合物生产平台，其具有克服现有细菌PHA生产系统的重复单元组成缺乏多样性和控制的潜力，并扩大PHA聚合物的应用数量。 拟议的研究和研究培训活动预计将对社会产生广泛的影响，从改进生物可降解和生物基聚合物合成科学到开发用于研究、工业和生物医学应用的新生物材料。 该项目将有助于减少美国对不可再生能源的依赖，如能源，材料生产和运输的化石燃料。 与本提案相关的研究本质上是跨学科的，将在多样化的培训环境中进行。 它还将为代表性不足的少数民族学生提供暑期研究经验，目的是增加传统上在科学和工程领域代表性不足的群体的大学毕业生人数。 由于该SusChEM项目的跨学科性质，CBET部门的生物技术，生物化学和生物工程计划的奖项由分子和细胞生物学部门的遗传机制计划以及材料研究部门的生物材料计划共同赞助。

1263905 - Nomura Polyhydroxyalkanoates (PHAs) are microbially produced, biobased, and biodegradable polymers that have a wide array of uses ranging from substitutes for non-biodegradable, petroleum-based plastics in bulk commodity products to biomedical applications. One of the factors that limits the widespread use of PHAs for more specialized applications is the lack of control over repeating unit compositions and by extension the inability to produce polymers with desired physical properties. The long-term goal of this research project is to genetically engineer E. coli for producing expanded classes of PHA materials with desirable material properties. PHAs comprised of repeating units of 3-5 carbon atoms are known as short-chain-length PHAs (SCL-PHAs) and tend to be thermoplastic in nature but lack toughness, while PHAs comprised of repeating units of 6-14 carbon atoms are known as medium-chain-length PHAs (MCL-PHAs) and tend to be elastomeric. It has been demonstrated in previous studies that SCL-MCL PHA copolymers that are comprised of 80-95% SCL and 5-20% MCL repeating units have material properties that are very similar to common petroleum-based plastics. The objective of this project is to further develop strains so that they can produce SCL-MCL PHA and PHA-co-Polylactic acid (PLA) copolymers with desirable material properties from the renewable sugar feedstocks, and to produce new PHA-co-PLA copolymers with specific repeating unit compositions from lactic acid and fatty acids. This will be accomplished with a combination of synthetic biology, metabolic engineering, protein engineering, and synthetic chemistry methods to improve PHA production. Successful completion of these studies will lead to novel polymer production platforms with the potential to overcome the lack of diversity and control over repeating unit compositions of existing bacterial PHA producing systems and expand the number of applications for PHA polymers. The proposed studies and research training activities are expected to have a broad impact on society, ranging from improving upon the science of biodegradable and biobased polymer synthesis to the development of new biomaterials for research, industrial, and biomedical applications. The project will contribute to reduce US dependency on non-renewable sources such as fossil fuels for energy, materials production, and transportation. The research associated with this proposal is intrinsically interdisciplinary in nature and will be performed in a diverse training environment. It will also provide summer research experiences for underrepresented minority students with a goal of increasing the number of college graduates from groups that are traditionally underrepresented in science and engineering. Due to the interdisciplinary nature of this SusChEM project the award from the Biotechnology, Biochemical, and Bioengineering Program of the CBET Division is co-sponsored by the Genetic Mechanisms Program of the Molecular and Cell Biology Division and by the Biomaterials Program of the Division of Materials Research.