School of Food Science and Technology, Jiangnan University, 214122 Wuxi, China.
Centre for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation (QAAFI), The University of Queensland, St Lucia, QLD, Australia.
Bioresour Technol. 2024 Oct;409:131187. doi: 10.1016/j.biortech.2024.131187. Epub 2024 Jul 31.
Metabolic engineering provides a powerful approach to efficiently produce valuable compounds, with the aid of emerging gene editing tools and diverse metabolic regulation strategies. However, apart from the current known biochemical pathway information, a variety of unclear constraints commonly limited the optimization space of cell phenotype. Hydroxytyrosol is an important phenolic compound that serves various industries with prominent health-beneficial properties. In this study, the inverse metabolic engineering based on metabolome analysis was customized and implemented to disclose the hidden rate-limiting steps and thus to improve hydroxytyrosol production in Saccharomyces cerevisiae (S. cerevisiae). The potential rate-limiting steps involved three modules that were eliminated individually via reinforcing and balancing metabolic flow, optimizing cofactor supply, and weakening the competitive pathways. Ultimately, a 118.53 % improvement in hydroxytyrosol production (639.84 mg/L) was achieved by inverse metabolic engineering.
代谢工程提供了一种强大的方法，通过新兴的基因编辑工具和多样化的代谢调控策略，高效地生产有价值的化合物。然而，除了当前已知的生化途径信息外，各种不明确的限制因素通常限制了细胞表型的优化空间。羟基酪醇是一种重要的酚类化合物，在各个行业中具有显著的健康益处。在本研究中，基于代谢组学分析的反向代谢工程被定制和实施，以揭示隐藏的限速步骤，从而提高酿酒酵母（Saccharomyces cerevisiae）中羟基酪醇的产量。潜在的限速步骤涉及三个模块，通过加强和平衡代谢流、优化辅助因子供应以及削弱竞争途径，分别消除了这些模块。最终，通过反向代谢工程实现了羟基酪醇产量提高 118.53%（639.84mg/L）。
