Biosynthesis via Synthetic Biology

通过合成生物学进行生物合成

• 批准号: 8828226
• 负责人: Huimin Zhao
• 金额: $ 31.41万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8828226
• 关键词: Acetyl Coenzyme A; Acyltransferase; Anabolism; Antibiotics; Antimalarials; Area; Binding Sites; Biological Factors; Coenzyme A; D-xylulose-5-phosphate; DNA; DNA Maintenance; DNA biosynthesis; Development; Engineering; Enzymes; Equilibrium; Escherichia coli; Esters; Fosfomycin; Frankia; Gene Expression; Genes; Goals; Libraries; Metabolic; Methods; Methyltransferase; Parasites; Pathway interactions; Phosphoenolpyruvate; Phosphonic Acids; Plasmids; Plasmodium falciparum; Production; Pseudomonas syringae; Research; Saccharomyces cerevisiae; Series; Source; Streptomyces; Streptomyces lividans; Substrate Specificity; Variant; analog; base; combinatorial; design; directed evolution; expression vector; genetic element; genome sequencing; in vitro Assay; metabolic engineering; metagenome; microbial; microorganism; mutant; novel; phosphonate; promoter; reconstitution; scaffold; synthetic biology

Microorganisms produce a myriad array of natural products or secondary metabolites that are of biomedical and biotechnological importance. However, the discovery and sustainable production of these compounds are often limited by our capability to manipulate the biosynthetic genes or clusters in either the native or the heterologous host. To overcome this key limitation in the natural product biosynthesis research area, the overall goal of the proposed research is to develop synthetic biology approaches for discovery, characterization, and engineering of phosphonic acid natural products in microorganisms. Specifically, we will focus on the engineering of the FR-900098 and fosfomycin biosynthetic pathways in heterologous hosts and development of new synthetic biology approaches for discovery of novel phosphonic acid natural products from sequenced genomes.

微生物产生无数的生物医学活性的天然产物或次级代谢产物， 和生物技术的重要性。然而，这些化合物的发现和可持续生产是非常困难的。 通常受限于我们操纵天然或非天然生物中的生物合成基因或簇的能力， 异源宿主为了克服天然产物生物合成研究领域的这一关键限制， 拟议研究的总体目标是开发用于发现的合成生物学方法， 表征和微生物中膦酸天然产物的工程化。具体来说，我们将 专注于FR-900098和磷霉素生物合成途径在异源宿主中的工程改造， 开发新的合成生物学方法，用于发现新的膦酸天然产物 基因组测序