Collaborative R&D Project for Production of High Value Unnatural Amino Acids by Exploiting Novel Phenylalanine Ammonia Lyase (PAL) Biocatalysts

非天然氨基酸具有合成和商业利益，因为它们通常掺入与制药工业相关的较大药物分子中。该项目将使用苯丙氨酸解氨酶（PAL）合成非天然苯丙氨酸衍生物。PAL酶具有广泛的底物耐受性，可能允许合成各种高价值的药物中间体，尽管野生型酶对非天然底物的转化率可能非常低。曼彻斯特大学AMRI和CoEBio3之间的这个合作项目旨在建立在以前的可行性项目中获得的知识的基础上，在该项目中，通过工程设计一种新的PAL酶，成功开发了一种实验室规模的生物催化路线，以获得高价值的非天然氨基酸。在此，提出了后续工作，以证明这种生物催化途径在商业上是可行的，并优于当前的生产工艺。然后，该项目旨在采用优化的生物催化路线，并将其转化为创新的平台技术，以可持续的方式合成更广泛的非天然氨基酸和相关化学品，同时与传统的石化路线具有商业竞争力。

Unnatural amino acids are of synthetic and commercial interest as they are commonly incorporated into larger drug molecules relevant to the pharmaceutical industry. This project will use the enzyme Phenylalanine Ammonia Lyase (PAL) for the synthesis of unnatural phenylalanine derivatives.PAL enzymes have a broad substrate tolerance, potentially allowing the synthesis of a wide range of high value pharmaceutical intermediates, although the conversion of unnatural substrates by the wild type enzyme can be very low. This collaborative project, between AMRI and CoEBio3 at the University of Manchester, aims to build upon the knowledge gained during a previous feasibility project, in which a laboratory scale biocatalytic route to a high value unnatural amino acid was successfully developed by engineering a new PAL enzyme. Here, follow on work is proposed to demonstrate that this biocatalytic route can be commercially viable and out-compete the current manufacturing process. The project then aims to take the optimised biocatalytic route and transform it into an innovative platform technology to synthesise a broader range of unnatural amino acids and related chemicals in a sustainable manner, whilst being commercially competitive with traditional petrochemical routes.