Abstract
Gamma-aminobutyric acid (GABA) is widely distributed in nature and considered a potent bioactive compound with numerous and important physiological functions, such as anti-hypertensive and antidepressant activities. There is an ever-growing demand for GABA production in recent years. Lactic acid bacteria (LAB) are one of the most important GABA producers because of their food-grade nature and potential of producing GABA-rich functional foods directly. In this paper, the GABA-producing LAB species, the biosynthesis pathway of GABA by LAB, and the research progress of glutamate decarboxylase (GAD), the key enzyme of GABA biosynthesis, were reviewed. Furthermore, GABA production enhancement strategies are reviewed, from optimization of culture conditions and genetic engineering to physiology-oriented engineering approaches and co-culture methods. The advances in both the molecular mechanisms of GABA biosynthesis and the technologies of synthetic biology and genetic engineering will promote GABA production of LAB to meet people’s demand for GABA. The aim of the review is to provide an insight of microbial engineering for improved production of GABA by LAB in the future.
Highlights
Gamma-aminobutyric acid (GABA) is a four-carbon free amino acid that is produced from l-glutamic acid by glutamate decarboxylase (GAD) and is widely present in microorganisms, plants, and animals [1]
The biosynthesis of GABA by microorganisms is performed by the glutamic acid decarboxylase (GAD, EC 4.1.1.15) system, which is composed of the GAD enzyme and glutamate/GABA antiporter GadC [29,30,31,32,33]
In order to resolve the discrepancy of optimal pH between GAD activity and cell growth, recombinant C. glutamicum strains were constructed by expressing E. coli GAD mutants with an expanded pH range activity; it provided a balanced condition for cell growth and GABA production
Summary
Gamma-aminobutyric acid (GABA) is a four-carbon free amino acid that is produced from l-glutamic acid by glutamate decarboxylase (GAD) and is widely present in microorganisms, plants, and animals [1]. Because of the generally recognized as safe (GRAS) status of LAB and their high application potential in the fermentation industry, GABA-producing LAB have received extensive attention in recent years. A large number of GABA-producing LAB were isolated from fermented food and used in the manufacturing of naturally health-oriented foods enriched with GABA. In view of the food-grade nature of LAB and their potential as a functional food, this paper will focus on the GABA-producing LAB. GABA production enhancement strategies are discussed, from optimization of culture conditions and genetic engineering to physiology-oriented engineering approaches and co-culture methods
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