Recent advances in production of 5-aminolevulinic acid using biological strategies

Abstract

5-Aminolevulinic acid (5-ALA) is the precursor for the biosynthesis of tetrapyrrole compounds and has broad applications in the medical and agricultural fields. Because of the disadvantages of chemical synthesis methods, microbial production of 5-ALA has drawn intensive attention and has been regarded as an alternative in the last years, especially with the rapid development of metabolic engineering and synthetic biology. In this mini-review, recent advances on the application and microbial production of 5-ALA using novel biological approaches (such as whole-cell enzymatic-transformation, metabolic pathway engineering and cell-free process) are described and discussed in detail. In addition, the challenges and prospects of synthetic biology are discussed.

The Dark Side: Photosensitizer Prodrugs

“…PDT is also a relevant tool for diagnosis in vivo, for instance to detect brain tumors [122], gliomas [123], endometriosis, intraepithelial lesions of the cervix, and lung cancer among others [124] Finally, the last described application of the 5-ALA compounds, far from the field of medicine, is related to farming for use as a fertilizer, herbicide, and insecticide [125,126], and also facilitating plant tolerance to salt and cold temperatures [88].…”

Enhancing 5‐aminolevulinic acid tolerance and production by engineering the antioxidant defense system of Escherichia coli

“…Recently, intensive studies have concentrated on engineering platform microbes for ALA production from inexpensive carbon sources. Escherichia coli and Corynebacterium glutamicum are the most studied chassis due to their clear genetic backgrounds and advanced metabolic engineering tools (Kang et al, ). Both E. coli and C. glutamicum possess the endogenous C5 pathway for ALA synthesis (Kang et al, ).…”

“…Escherichia coli and Corynebacterium glutamicum are the most studied chassis due to their clear genetic backgrounds and advanced metabolic engineering tools (Kang et al, ). Both E. coli and C. glutamicum possess the endogenous C5 pathway for ALA synthesis (Kang et al, ). Kang et al first strengthened the C5 pathway and ALA export in E. coli .…”

“…Although microbial production of ALA has been significantly improved during the past few years, there is still a big gap between the production levels of ALA and other amino acids, such as glutamate and lysine that are produced at over 100 g/L (Datsenko & Wanner, ). The present research efforts mainly focus on engineering of enzymes and metabolic pathways involved in ALA biosynthesis (Kang et al, ). The cellular response and tolerance to high concentration of ALA become the missing pieces in revealing the limiting factors for high‐level ALA production.…”

Efficient bioproduction of 5-aminolevulinic acid, a promising biostimulant and nutrient, from renewable bioresources by engineered Corynebacterium glutamicum

“…Chemical synthesis is the primary method for industrial production of 5-ALA. Six chemically synthetic methods have been reported, whereas the complicated reaction and purification steps and low yield cause the high price of 5-ALA, which seriously limits its widespread use in agriculture [1]. Bioproduction of 5-ALA holds the potential to simplify the production process and lower the cost, and thus has received growing attention recently [9,10]. Although some algae and photosynthetic bacteria are capable to synthesize 5-ALA naturally, the production levels are not satisfactory and these microorganisms are usually difficult to engineer [11,12].…”