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Advances in the Microbial Synthesis of 5-Hydroxytryptophan.

Xin-Xin Liu, Bin Zhang, Lian-Zhong Ai
Review Frontiers in bioengineering and biotechnology 2021 18 citas
PubMed DOI PDF
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narrative_review

                        

                        
                        
                        
                        
                    

                    

                        
                        

                            
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Advances in the Microbial Synthesis of 5-Hydroxytryptophan. None

                        

                        
                        
                        

                            
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                                    Positive
                                
                            

                        

                        
                        

                            
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High

                        

                        
                    

                

            

        

        

        
        
        

            

  
Abstract





            

                
5-Hydroxytryptophan (5-HTP) plays an important role in the regulation of emotion, behavior, sleep, pain, body temperature, and other physiological functions. It is used in the treatment of depression, insomnia, migraine, and other diseases. Due to a lack of effective biosynthesis methods, 5-HTP is mainly obtained by natural extraction, which has been unable to meet the needs of the market. Through the directed evolution of enzymes and the introduction of substrate supply pathways, 5-HTP biosynthesis and yield increase have been realized. This review provides examples that illustrate the production mode of 5-HTP and the latest progress in microbial synthesis.

            

        

        

        
        

        
        
        

            

  
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Figures





            

                
                
                    
                    

                        Biosynthetic pathways for 5-hydroxytryptophan production in microbial systems, showing the tryptophan hydroxylation route and alternative enzymatic strategies. Key enzymes including tryptophan hydroxylase and pterin-dependent monooxygenases are mapped with their cofactor requirements.
                    

                    
                    

                        
Figure 1

                        
                        
Biosynthetic pathways for 5-hydroxytryptophan production in microbial systems, showing the tryptophan hydroxylation route and alternative enzymatic strategies. Key enzymes including tryptophan hydroxylase and pterin-dependent monooxygenases are mapped with their cofactor requirements.

                        
                        
                        diagram
                        
                    

                
                
                
                    
                    

                        Summary of metabolic engineering strategies applied to improve microbial 5-HTP production, including directed enzyme evolution, cofactor supply enhancement, and precursor pathway optimization. Progressive improvements in titer and yield across different approaches are compared.
                    

                    
                    

                        
Figure 2

                        
                        
Summary of metabolic engineering strategies applied to improve microbial 5-HTP production, including directed enzyme evolution, cofactor supply enhancement, and precursor pathway optimization. Progressive improvements in titer and yield across different approaches are compared.

                        
                        
                        diagram
                        
                    

                
                
            

        

        

        
        
        

            

  
Tables





            

                
                

                    

                        
Table 1

                        
                    

                    

                        
StrainsModulationsTiter (g/L)CultivationReferences
E. coliOverexpression of mutant PAH,0.1762Shake flask; Supplementation of BH4 and 5 mM L-trpKino et al., 2009; Hara and Kino, 2013
E. coliOverexpression of mutant PAH; Insertion of BH4 regeneration pathway; Insertion of glucose dehydrogenase from Bacillus subtilis0.55Shake flask; Supplementation of 5 mM L-TrpHara and Kino, 2013
E. coliMutation of PAH from Xanthomonas campestris; Co-expression of MH4 regeneration pathway and L-trp synthesis pathway0.1529Shake flask; Supplementation of glucoseLin et al., 2014
E. coliMutation of the PAH from Xanthomonas campestris; Co-expression of MH4 regeneration and the L-trp synthesis pathway; Transformation into an L-trp high-yield strain0.962Fed-batchMora-Villalobos and Zeng, 2018
E. coliMutation of phenylalanine-4-hydroxylases (P4Hs); Deletion of the pheA, tyrA, and tnaA genes1.1–1.2Shake flask; Supplementation of 2 g/L L-TrpLin et al., 2014
E. coliMutation of AAAH; Insertion of the human BH4 regeneration pathway; Disruption of tryptophanase0.55Supplementation of 1 g/L L-TrpMora-Villalobos and Zeng, 2017
E. coliExpression of a truncated human TPH2; Reconstitution of the BH4 synthesis and regeneration pathway; Modulation of the plasmid copy number and promoter strength; Modulation of different modules' expression levels1.3Shake flask; Glycerol as carbon sourceWang et al., 2018
E. coliSame as the previous line5.1Fed-batch; Glycerol as carbon sourceWang et al., 2018
E. coliExpression of a truncated human TPH2; Reconstitution of the BH4 synthesis and regeneration pathway; Modulation of the plasmid copy number and promoter strength; Modulation of the relative expression levels among different modules; Designing promoter strength to increase tryptophan production1.61Shake flask; Glycerol as carbon sourceXu et al., 2020

                    

                

                
            

        

        

        
        
        

            

  
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Used In Evidence Reviews





            

                
                
                    

                        A

                        
                            Tryptophan para Insomnio
                        
                    

                    
                
                
                
                    

                        B

                        
                            5-HTP para Insomnio
                        
                    

                    
                
                
            

        

        

        
        
        

            

  
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