Manipulation of tRNA to Enhance Biologic Production

生物制剂生产是一个价值数十亿美元的产业，提供了大量的医疗保健福利和无限的扩张机会。在BBSRC工业生物技术催化剂早期翻译奖的资助下，我的实验室开发了一种新的合成生物学策略，可以在原理验证实验中提高产品质量和产量。寻求后续资金，以支持与跨国公司合作，在工业生产条件下使用专有平台和生物制剂对我们的战略进行结结性测试。我们的策略是基于测量和操纵生物合成所需的trna。一些tRNA比其他tRNA丰富得多，单个tRNA的稀缺性会限制其产生。然而，trna的相对水平尚未在工业环境中测量。我们建议通过补充tRNA和改进密码子优化来填补这一关键知识空白和弥补缺陷。

Biologic production is a multibillion dollar industry, providing substantial healthcare benefits and unlimited opportunity for expansion. Funded by a BBSRC Industrial Biotechnology Catalyst Early Stage Translation Award, my lab developed a novel synthetic biology strategy that boosts product quality and yield in proof-of-principle experiments. Follow-on funding is sought to support conclusive tests of our strategy using proprietary platforms and biologics under conditions of industrial production, in collaborations with multinational companies. Our strategy is based on measuring and manipulating tRNAs required for biologic synthesis. Some tRNAs are much more abundant than others and scarcity of a single tRNA can restrict production. However, relative levels of tRNAs have not been measured in industrial contexts. We propose to fill this key knowledge gap and remediate deficiencies by tRNA supplementation and improved codon optimization.