Abstract:

Lactic acid bacteria (LAB) are a group of Gram-positive bacteria that metabolize soluble carbohydrates to produce lactate as the main metabolite. Certain LAB strains have a long history of use in fermented foods and are generally considered as safe microorganisms. At the same time, LAB are normal commensal bacteria of the human body and have been shown to exert beneficial effects on the host, such as regulating the balance of intestinal and skin microecology and enhancing the body's immunity. At present, the addition of LAB and its active metabolites to skin care products could produce moisturizing, antioxidant, and allergy-reduction effects, which have been recognized by consumers. The roles of some lactic acid bacteria in alleviating and treating skin diseases are also supported by more and more experimental data. With the rapid development of genetic tools, LAB have been explored to effectively produce high-value-added food and biomedical products such as organic acids, alcohols and exopolysaccharides. Moreover, recent advances in synthetic biology have realized engineered LAB cells to deliver therapeutic molecules in response to disease signals, showing attractive application prospects for disease therapy in situ. In the field of skincare, LAB are appealing chassis for the production of bioactive substances of skin and also as biotherapy carriers of wound treatment, as the food-safe status of LAB strains. In this review, we summarize the genetic operation systems established in LAB, from genetic accessibility to gene expression systems, and highlight the emerging genome editing techniques for manipulating the LAB genome. In addition, we introduce the research progress of the production of moisturizing factors and antioxidants using LAB as a cell factory. Finally, we summarize the feasibility of targeted drug delivery by engineered LAB for skin wound heal and prevention of infection by pathogenic bacteria, aiming at providing a reference for applying LAB in skin health.

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

摘要：

乳酸菌在发酵食品中有着悠久的使用历史，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，具有调解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