乳酸菌的合成生物学工具及在合成益肤因子中的应用

doi:10.12211/2096-8280.2024-071

摘要/Abstract

摘要：

乳酸菌在发酵食品中的使用有着悠久历史，一些菌种被认为是安全级微生物。乳酸菌也是人体正常的共生菌，具有调节肠道和皮肤微生态的菌群平衡、增强机体免疫力等有益作用。当前，乳酸菌及其产生的活性代谢产物添加到护肤品中产生保湿、抗氧化和减轻过敏等效果得到了消费者认可，而一些乳酸菌在缓解和治疗皮肤疾病方面的作用也有越来越多的数据支持。基于此，利用乳酸菌作为底盘生产护肤活性物质或作为皮肤修复的生物治疗载体具有广阔的应用前景。本文首先总结了在乳酸菌中建立的遗传操作系统，着重关注遗传可及性、基因表达系统和基因组编辑技术，然后总结了乳酸菌作为细胞工厂生产保湿因子和抗氧化产物的研究进展，最后介绍了工程乳酸菌针对皮肤损伤进行靶向递药的可行性，旨在为乳酸菌应用于皮肤健康领域提供借鉴。

关键词: 乳酸菌, 合成生物学, 遗传操作系统, 皮肤修复, 活菌药物

Abstract:

Lactic acid bacteria (LABs) are a group of Gram-positive bacteria that metabolize soluble carbohydrates to produce lactate as the main metabolite. Certain LABs have a long history of use in fermented foods and are generally considered as safe. On the other hand, LABs are commensal bacteria of the human body and have been shown to exert beneficial effect on the host, such as regulating the balance of intestinal and skin microecology and enhancing the body's immunity. At present, the addition of LABs and their active metabolites to skin care products could enhance moisturizing, antioxidant, and allergy-reduction effect, which have been accepted by consumers. The roles of LABs in treating skin diseases are also supported by more and more experimental data. With the rapid development of genetic tools, LABs have been explored to effectively produce value-added food and biomedical products such as organic acids, alcohols, and exopolysaccharides. Moreover, recent advances in synthetic biology have been used to engineer LABs for delivering therapeutic molecules in response to disease signals, showing attractive application prospect for disease therapy insitu. In the field of skincare, LABs are an attractive chassis for being engineered to produce bioactive substances for skincare and also as biotherapy carriers for wound treatment, as the food-safe status of LABs. In this review, we summarize the genetic operation systems established for LABs, from genetic accessibility to gene expression systems, and highlight the emerging genome editing techniques for manipulating their genomes. In addition, we comment research progress in producing moisturizing factors and antioxidants using LABs as cell factories. Finally, we expect the feasibility of targeted drug delivery by engineered LABs for healing skin wound and the prevention of infection by pathogenic bacteria, aiming at providing a reference for applying LABs in skin health.

Key words: lactic acid bacteria, synthetic biology, genetic operation systems, skin repair, live biotherapeutic product

中图分类号:

Q939.9

郭婷婷, 韩湘凝, 黄熙婷, 张婷婷, 孔健. 乳酸菌的合成生物学工具及在合成益肤因子中的应用[J]. 合成生物学, 2025, 6(2): 320-333.

GUO Tingting, HAN Xiangning, HUANG Xiting, ZHANG Tingting, KONG Jian. Advances in synthetic biology tools for lactic acid bacteria and their application in the development of skin beneficial products[J]. Synthetic Biology Journal, 2025, 6(2): 320-333.

图/表 3

图1 乳酸菌中常用的基因诱导表达系统工作示意图

Fig. 1 Schematic diagram of commonly used gene expression systems for lactic acid bacteria

图2 乳酸菌中3种基因组改造方法原理［55］

Fig. 2 Schematic diagram of methods for genome engineering in lactic acid bacteria［55］

图3 利用工程乳酸菌原位修复皮肤伤口的示意图

Fig. 3 Strategies for repairing cutaneous wounds in situ by engineered lactic acid bacteria

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