SBIR Phase I: Chemoenzymatic Production of Innovative Sesquiterpene-Based Fragrance Libraries

这个小型企业创新研究(SBIR)第一阶段研究项目旨在开发一个基于酵母的平台，用于生成新的倍半萜化合物以及商业上无法获得的倍半萜支架。这项技术结合了代谢、蛋白质和生物化学的方法来产生定义的倍半萜支架，这些支架又被用来使用组合化学来产生有趣的化合物库。生成的化合物对香料行业具有商业价值，但也可以筛选与医学相关的特性。甲戊酸和非甲戊酸途径是目前已知的唯一用于合成异戊烯焦磷酸的途径，焦磷酸是异戊二烯(萜烯)的前体之一，异戊二烯(萜烯)是结构最多样化的一类生物化合物。这些前体通过一系列的酶反应转化为萜烯。这项拟议的技术旨在利用对萜类的生物化学和酶学的了解来开发一种工艺，使数千种具有有趣性质和巨大商业价值的新倍半萜的生产成为可能。

This Small Business Innovation Research (SBIR) Phase I research project aims to develop a yeast-based platform for the generation of novel sesquiterpene compounds, as well as commercially unavailable sesquiterpene scaffolds. The technique combines metabolic, protein and biochemical approaches to produce defined sesquiterpene scaffolds, which are in turn, used to produce libraries of interesting compounds using combinatorial chemistry. The generated compounds are commercially valuable to the fragrance industry, but could also be screened for medically relevant properties. The mevalonate and non-mevalonate pathways are currently the only ones known to be used for the synthesis of isopentenyl pyrophosphate, one of the precursors to isoprenoids (terpenes), the most structurally diverse class of biological compounds. These precursors are converted to the terpenes through a series of enzymatic reactions. The proposed technology aims to leverage the understanding of the biochemistry and enzymology of the terpenes to develop a process that enables the production of thousands of new sesqueterpenes with interesting properties and great commercial value.