Institute of Applied Microbiology-iAMB, Aachen Biology and Biotechnology-ABBt, RWTH Aachen University, Worringer Weg 1, Aachen, 52074, Germany.
Genome Institute of Singapore, 60 Biopolis Street, Genome, 03-01, Singapore, 138672, Singapore.
BMC Biotechnol. 2021 Mar 15;21(1):23. doi: 10.1186/s12896-021-00675-w.
Ogataea polymorpha is a thermotolerant, methylotrophic yeast with significant industrial applications. While previously mainly used for protein synthesis, it also holds promise for producing platform chemicals. O. polymorpha has the distinct advantage of using methanol as a substrate, which could be potentially derived from carbon capture and utilization streams. Full development of the organism into a production strain and estimation of the metabolic capabilities require additional strain design, guided by metabolic modeling with a genome-scale metabolic model. However, to date, no genome-scale metabolic model is available for O. polymorpha.
To overcome this limitation, we used a published reconstruction of the closely related yeast Komagataella phaffii as a reference and corrected reactions based on KEGG and MGOB annotation. Additionally, we conducted phenotype microarray experiments to test the suitability of 190 substrates as carbon sources. Over three-quarter of the substrate use was correctly reproduced by the model and 27 new substrates were added, that were not present in the K. phaffii reference model.
The developed genome-scale metabolic model of O. polymorpha will support the engineering of synthetic metabolic capabilities and enable the optimization of production processes, thereby supporting a sustainable future methanol economy.
Ogataea polymorpha 是一种耐热、甲醇营养型酵母，具有重要的工业应用价值。虽然它以前主要用于蛋白质合成，但在生产平台化学品方面也具有潜力。O. polymorpha 的一个显著优势是可以使用甲醇作为底物，而甲醇可以潜在地从碳捕获和利用流中获得。要将该生物体充分开发为生产菌株并评估其代谢能力，需要在代谢建模的指导下进行进一步的菌株设计，使用基因组尺度的代谢模型进行代谢建模。然而，迄今为止，还没有用于 O. polymorpha 的基因组尺度代谢模型。
为了克服这一限制，我们使用了已发表的与密切相关的酵母 Komagataella phaffii 的重建作为参考，并根据 KEGG 和 MGOB 注释校正了反应。此外，我们还进行了表型微阵列实验，以测试 190 种底物作为碳源的适用性。模型正确再现了超过四分之三的底物利用情况，并添加了 27 种新的底物，这些底物在 K. phaffii 参考模型中不存在。
开发的 O. polymorpha 基因组尺度代谢模型将支持合成代谢能力的工程设计，并能够优化生产工艺，从而支持可持续的甲醇经济未来。
