Li Xu, Krysiak-Baltyn Konrad, Richards Luke, Jarrold Ailsa, Stevens Geoffrey W, Bowser Tim, Speight Robert E, Gras Sally L
Department of Chemical Engineering, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
ACS Omega. 2020 Apr 3;5(16):9339-9347. doi: 10.1021/acsomega.0c00282. eCollection 2020 Apr 28.
An enzymatic biosynthesis approach is described for codeine, the most widely used medicinal opiate, providing a more environmentally sustainable alternative to current chemical conversion, with yields and productivity compatible with industrial production. strains were engineered to express key enzymes from poppy, including the recently discovered neopinone isomerase, producing codeine from thebaine. We show that compartmentalization of these enzymes in different cells is an effective strategy that allows active spatial and temporal control of reactions, increasing yield and volumetric productivity and reducing byproduct generation. Codeine is produced at a yield of 64% and a volumetric productivity of 0.19 g/(L·h), providing the basis for an industrially applicable aqueous whole-cell biotransformation process. This approach could be used to redirect thebaine-rich feedstocks arising from the U.S. reduction of opioid manufacturing quotas or applied to enable total biosynthesis and may have broader applicability to other medicinal plant compounds.
本文描述了一种用于生产可待因（最广泛使用的药用阿片类药物）的酶促生物合成方法，该方法为当前的化学转化提供了一种更具环境可持续性的替代方案，其产量和生产率与工业生产相兼容。对菌株进行工程改造，使其表达来自罂粟的关键酶，包括最近发现的新皮诺宁异构酶，从而从蒂巴因生产可待因。我们表明，将这些酶分隔在不同细胞中是一种有效的策略，能够对反应进行有效的时空控制，提高产量和体积生产率，并减少副产物的产生。可待因的产量为64%，体积生产率为0.19 g/(L·h)，为工业适用的全细胞水相生物转化过程奠定了基础。这种方法可用于重新利用因美国减少阿片类药物生产配额而产生的富含蒂巴因的原料，或用于实现完全生物合成，并且可能对其他药用植物化合物具有更广泛的适用性。
