Advances in Flavonoid and Derivative Biosynthesis: Systematic Strategies for the Construction of Yeast Cell Factories.

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS ACS Synthetic Biology Pub Date : 2024-09-20 Epub Date: 2024-08-15 DOI:10.1021/acssynbio.4c00383

Jian Wang, Cheng Chen, Qi Guo, Yang Gu, Tian-Qiong Shi

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Abstract

Flavonoids, a significant group of natural polyphenolic compounds, possess a broad spectrum of pharmacological effects. Recent advances in the systematic metabolic engineering of yeast cell factories (YCFs) provide new opportunities for enhanced flavonoid production. Herein, we outline the latest research progress on typical flavonoid products in YCFs. Advanced engineering strategies involved in flavonoid biosynthesis are discussed in detail, including enhancing precursor supply, cofactor engineering, optimizing core pathways, eliminating competitive pathways, relieving transport limitations, and dynamic regulation. Additionally, we highlight the existing problems in the biosynthesis of flavonoid glucosides in yeast, such as endogenous degradation of flavonoid glycosides, substrate promiscuity of UDP-glycosyltransferases, and an insufficient supply of UDP-sugars, with summaries on the corresponding solutions. Discussions also cover other typical postmodifications like prenylation and methylation, and the recent biosynthesis of complex flavonoid compounds in yeast. Finally, a series of advanced technologies are envisioned, i.e., semirational enzyme engineering, ML/DL algorithn, and systems biology, with the aspiration of achieving large-scale industrial production of flavonoid compounds in the future.

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黄酮类化合物和衍生物生物合成的进展：构建酵母细胞工厂的系统策略》。

类黄酮是一类重要的天然多酚化合物，具有广泛的药理作用。酵母细胞工厂（YCF）系统代谢工程的最新进展为提高类黄酮的产量提供了新的机遇。在此，我们将概述酵母细胞工厂中典型类黄酮产品的最新研究进展。我们详细讨论了黄酮类化合物生物合成所涉及的先进工程策略，包括加强前体供应、辅助因子工程、优化核心途径、消除竞争途径、缓解运输限制以及动态调控。此外，我们还强调了酵母中黄酮苷生物合成过程中存在的问题，如黄酮苷的内源性降解、UDP-糖基转移酶底物的杂合性、UDP-糖的供应不足等，并总结了相应的解决方案。讨论还包括其他典型的后修饰，如前酰化和甲基化，以及最近在酵母中复杂类黄酮化合物的生物合成。最后，展望了一系列先进技术，即半理性酶工程、ML/DL 算法和系统生物学，以期在未来实现黄酮类化合物的大规模工业化生产。

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来源期刊

ACS Synthetic Biology 生物-

CiteScore

8.00

自引率

10.60%

发文量

380

审稿时长

6-12 weeks

期刊介绍： The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.