Huang Chenxi, Cheng Lianghui
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China.
Int J Mol Sci. 2025 Aug 22;26(17):8119. doi: 10.3390/ijms26178119.
Bioactive peptides encrypted in bovine β-casein display diverse physiological functions, including antihypertensive, antioxidative, antimicrobial, and immunomodulatory activities. These peptides are normally released during gastrointestinal digestion or microbial fermentation, especially by proteolytic systems of lactic acid bacteria (LAB). However, peptide yields vary widely among LAB strains, reflecting strain-specific protease repertoires. To overcome these limitations, the scientific goal of this study is to provide a comprehensive synthesis of how synthetic biology, molecular biotechnology, and systems-level approaches can be leveraged to enhance the targeted discovery and production of β-casein-derived bioactive peptides. Genome engineering tools such as clustered regularly interspaced short palindromic repeats associated system (CRISPR/Cas) systems have been applied to modulate gene expression and metabolic flux in LAB, while inducible expression platforms allow on-demand peptide production. Additionally, cell-free systems based on LAB lysates further provide rapid prototyping for high-throughput screening. Finally, multi-omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, further help pinpoint regulatory bottlenecks and facilitate rational strain optimization. This review provides a comprehensive overview of bioactive peptides derived from bovine β-casein and highlights recent progress in LAB-based strategies-both natural and engineered-for their efficient release. These advances pave the way for developing next-generation functional fermented foods enriched with targeted bioactivities.
牛β-酪蛋白中加密的生物活性肽具有多种生理功能，包括抗高血压、抗氧化、抗菌和免疫调节活性。这些肽通常在胃肠道消化或微生物发酵过程中释放，尤其是通过乳酸菌（LAB）的蛋白水解系统。然而，不同LAB菌株的肽产量差异很大，这反映了菌株特异性的蛋白酶库。为了克服这些限制，本研究的科学目标是全面综合阐述如何利用合成生物学、分子生物技术和系统水平方法来加强β-酪蛋白衍生生物活性肽的靶向发现和生产。诸如成簇规律间隔短回文重复序列相关系统（CRISPR/Cas）系统等基因组工程工具已被应用于调节LAB中的基因表达和代谢通量，而诱导表达平台则允许按需生产肽。此外，基于LAB裂解物的无细胞系统进一步为高通量筛选提供了快速原型。最后，包括基因组学、转录组学、蛋白质组学和代谢组学在内的多组学方法进一步有助于查明调控瓶颈并促进合理的菌株优化。本综述全面概述了源自牛β-酪蛋白的生物活性肽，并强调了基于LAB的策略（包括天然和工程策略）在高效释放这些肽方面的最新进展。这些进展为开发富含靶向生物活性的下一代功能性发酵食品铺平了道路。
