Plant terpenoids: Deciphering metabolic pathways and improving production in microbes

植物萜类化合物：破译代谢途径并提高微生物的产量

• 批准号: 10714595
• 负责人: Zhen Wang
• 金额: $ 39.88万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714595
• 关键词: Acceleration; Biochemical; Biological Assay; Biomanufacturing; Digitalis (genus); Engineering; Gene Cluster; Genomics; Knowledge; Life; Medicine; Metabolic Pathway; Methods; Microbe; Millet; Mining; Pathway interactions; Plant Extracts; Plant Genome; Plants; Prevalence; Production; Productivity; Public Health; Research; Route; Saffron; Source; Terpenes; Time; Work; Yeasts; analog; cost effective; human disease; improved; metabolomics; novel; prevent; programs; reconstitution; transcriptomics

Beyond their prevalence in everyday life, many plant terpenoids have life-saving medicinal applications for a variety of human diseases. Despite their clear medicinal importance, it remains unclear how plants synthesize most plant terpneoids. This knowledge gap prevents us from developing a better method to access terpenoids since medicinal terpenoids are extracted from plants with meager yields. This research program aims to accelerate the identification of plant terpenoid biosynthetic pathways and to improve plant terpenoid production in microbes. Synthesizing plant terpenoids in microbes is a far more cost-effective approach as it can significantly enhance terpenoid productivity and shorten production time. We developed an integrated workflow capable of high-throughput characterization of multiple plant terpenoid pathways in parallel. This workflow combines genomic mining, transcriptomic analysis, metabolomics, and biochemical assays for terpenoid pathway elucidation followed by pathway reconstitution in engineered microbes for high-titer terpenoid production. Our workflow is unique in that it includes gene clusters in plant genomes as an untapped source for uncovering novel plant biosynthetic pathways. Another unique feature of our workflow is that we use a highly engineered yeast strain as a platform to produce plant specialized terpenoids. This highly productive platform strain sets the stage for cost-effective production of any of the >80,000 terpenoids and infinite numbers of terpenoid analogs. In this research program, we will apply this workflow to decipher multiple plant terpenoid pathways, including valuable mono-, di-, sesqui-, tri-, and tetra-terpenoid synthetic routes in foxglove, millet, crocus, and other plant species. Progress from the proposed work will advance fundamental knowledge regarding how plants synthesize medicinally important or biologically active terpenoids. It will also transform the biomanufacturing of plant-based medicines for renewable and cost-effective production.

除了在日常生活中普遍存在外，许多植物萜类化合物还具有挽救生命的药用价值