SBIR Phase I: Enzymatic Synthesis of Insect Pheromones

这个小企业创新研究第一阶段项目的更广泛的影响/商业潜力是农业害虫控制的突破。Provivi公司（Provivi）打算开发新型生物合成技术来生产昆虫信息素，即昆虫用于交流的化学物质。基于信息素的昆虫控制可以满足以下未满足的需求：（1）安全性、生物可降解性和在产品上不留残留物;（2）不干扰有益昆虫（例如蜜蜂和瓢虫）;（3）不导致杀虫剂抗性;（4）并且用作现有害虫管理策略的补充。虽然信息素在作物保护方面的潜力早已被认识到，但其高合成成本阻碍了广泛采用。Provivi？该技术旨在使信息素的合成成本大大降低。 这有可能改变农民通过采用信息素解决方案而不是传统杀虫剂来控制有害昆虫的方式。从商业角度来看，通过降低合成成本，Provivi信息素产品可以立即进入现有的信息素市场，并最终渗透到目前只有传统杀虫剂才能为农民负担得起的市场。该I期研究计划的目标是（1）证明一类昆虫信息素合成的生物合成方法，（2）鉴定具有足够活性的酶以保证进一步开发，以及（3）定量生物催化性能以生成拟议合成路线的工艺模型。所提出的信息素合成路线的核心是生物催化转化，其在现有的酶文献中没有描述。该项目旨在通过筛选已知催化类似反应的酶家族成员来鉴定能够支持这种新反应的酶。使用最好的酶变体，该项目将通过对市场上的昆虫信息素进行克级合成来证明该公司合成路线的可行性。通过进行克级合成，将有助于确定生物催化剂反应参数，包括产率、生产率、产物滴度和副产物滴度。这些参数将允许开发合成路线的详细工艺模型，并评估所提出的技术能够降低合成成本。

The broader impact/commercial potential of this Small Business Innovation Research Phase I project is an insect pest control breakthrough for the agricultural industry. Provivi, Inc. (Provivi) intends to develop novel biosynthesis technology for producing insect pheromones, i.e. chemicals that insects use for communication. Pheromone based insect control can fulfill the following unmet needs: (1) safety, biodegradability, and leaving no residues on products (2) not interfering with beneficial insects (e.g. bees and ladybugs), (3) not resulting in insecticide resistance, (4) and serve as a complement to existing pest management strategies. While pheromones have been long recognized for their potential in crop protection, their high synthesis costs have prevented broad adoption. Provivi?s technology aims to enable a dramatically lower cost synthesis of pheromones. This has the potential to change how farmers control damaging insects by adopting pheromone solutions in favor of traditional insecticides. From a commercial perspective, by lowering the cost of synthesis, Provivi pheromone products can immediately enter existing pheromone markets, and ultimately penetrate markets for which currently only traditional insecticides are affordable to farmers. The objectives of this Phase I research program are (1) the demonstration of a biosynthetic approach to the synthesis of a class of insect pheromones, (2) the identification of enzymes with sufficient activity to warrant further development and, (3) quantifications of the biocatalysis performance for generating a process model of the proposed synthesis route. At the heart of the proposed pheromone synthesis route is a biocatalytic transformation that has not been described in the existing enzyme literature. This project aims to identify enzymes capable of supporting this novel reaction by screening members of enzyme families that are known to catalyze similar reactions. Using the best identified enzyme variant, this project will demonstrate the feasibility of the company's synthesis route by performing a gram-scale synthesis of an in-market insect pheromone. By performing the gram-scale synthesis, it will help to determine the biocatalyst reaction parameters including yield, productivity, product titer and byproduct titers. These parameters will allow the development of a detailed process model of the synthesis route and assess the synthesis cost reduction enabled by the proposed technology.