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

这项小企业创新研究（SBIR）一期研究项目旨在开发一种基于酵母的平台，用于生成新型倍半萜化合物，以及商业上不可用的倍半萜支架。该技术结合了代谢、蛋白质和生化方法来生产确定的倍半萜支架，这些支架反过来又用于使用组合化学产生有趣的化合物文库。所产生的化合物对香料工业具有商业价值，但也可以用于筛选与医学相关的特性。甲基戊酸和非甲基戊酸途径是目前已知的唯一用于合成焦磷酸异戊烯基的途径，焦磷酸异戊烯基是类异戊二烯（萜）的前体之一，是结构最多样化的一类生物化合物。这些前体通过一系列酶促反应转化为萜烯。提出的技术旨在利用对萜烯的生物化学和酶学的理解来开发一种工艺，使生产数千种具有有趣性质和巨大商业价值的新倍半萜烯成为可能。

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.