Manipulation of tRNA to Enhance Biologic Production

生物生产是一个价值数十亿美元的行业，提供了巨大的医疗保健效益和无限的扩张机会。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，在原理验证实验中提高了产品质量和产量。寻求后续资金，以支持在工业生产条件下，与跨国公司合作，使用专有平台和生物制品对我们的战略进行决定性测试。我们的策略是基于测量和操作生物合成所需的tRNA。一些tRNA比另一些要丰富得多，单个tRNA的稀缺可能会限制生产。然而，tRNAs的相对水平尚未在工业背景下测量。我们建议通过tRNA补充和改进的密码子优化来填补这一关键知识缺口并弥补缺陷。

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.