Efficient Biosynthesis of (2S)-Naringenin from p-Coumaric Acid in Saccharomyces cerevisiae

Gao, Song; Lyu, Yunbin; Zeng, Weizhu; Du, Guocheng; Zhou, Jingwen; Chen, Jian

doi:10.1021/acs.jafc.9b05218

Cited by 75 publications

(58 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other strategies have been used to improve steps which are bottlenecks in the pathway, such as the reactions catalysed by the naringenin chalcone synthase, or by a cytochrome P 450 monooxygenase, which putatively enhances the cinnamoyl-4-hydroxylase activity [ 104 ]. This was achieved by modifying the promoters to enhance the induction by xylose of the expression of the genes [ 106 , 107 ], or by increasing the genes copy number [ 108 , 109 , 110 ]. The best naringenin production reached 1210 mg/L in a bioreactor after supplementing the cultures with p -coumaric acid [ 109 ].…”

Section: Heterologous Production Of Naringenin In Yeasts: Biotechnological Applicationsmentioning

confidence: 99%

Comparative Molecular Mechanisms of Biosynthesis of Naringenin and Related Chalcones in Actinobacteria and Plants: Relevance for the Obtention of Potent Bioactive Metabolites

Martı́n

Liras

2022

Antibiotics

View full text Add to dashboard Cite

Naringenin and its glycosylated derivative naringin are flavonoids that are synthesized by the phenylpropanoid pathway in plants. We found that naringenin is also formed by the actinobacterium Streptomyces clavuligerus, a well-known microorganism used to industrially produce clavulanic acid. The production of naringenin in S. clavuligerus involves a chalcone synthase that uses p-coumaric as a starter unit and a P450 monoxygenase, encoded by two adjacent genes (ncs-ncyP). The p-coumaric acid starter unit is formed by a tyrosine ammonia lyase encoded by an unlinked, tal, gene. Deletion and complementation studies demonstrate that these three genes are required for biosynthesis of naringenin in S. clavuligerus. Other actinobacteria chalcone synthases use caffeic acid, ferulic acid, sinapic acid or benzoic acid as starter units in the formation of different antibiotics and antitumor agents. The biosynthesis of naringenin is restricted to a few Streptomycess species and the encoding gene cluster is present also in some Saccharotrix and Kitasatospora species. Phylogenetic comparison of S. clavuligerus naringenin chalcone synthase with homologous proteins of other actinobacteria reveal that this protein is closely related to chalcone synthases that use malonyl-CoA as a starter unit for the formation of red-brown pigment. The function of the core enzymes in the pathway, such as the chalcone synthase and the tyrosine ammonia lyase, is conserved in plants and actinobacteria. However, S. clavuligerus use a P450 monooxygenase proposed to complete the cyclization step of the naringenin chalcone, whereas this reaction in plants is performed by a chalcone isomerase. Comparison of the plant and S. clavuligerus chalcone synthases indicates that they have not been transmitted between these organisms by a recent horizontal gene transfer phenomenon. We provide a comprehensive view of the molecular genetics and biochemistry of chalcone synthases and their impact on the development of antibacterial and antitumor compounds. These advances allow new bioactive compounds to be obtained using combinatorial strategies. In addition, processes of heterologous expression and bioconversion for the production of naringenin and naringenin-derived compounds in yeasts are described.

show abstract

Section: Heterologous Production Of Naringenin In Yeasts: Biotechnological Applicationsmentioning

confidence: 99%

Comparative Molecular Mechanisms of Biosynthesis of Naringenin and Related Chalcones in Actinobacteria and Plants: Relevance for the Obtention of Potent Bioactive Metabolites

Martı́n

Liras

2022

Antibiotics

View full text Add to dashboard Cite

show abstract

“…It was believed that the low titers were limited by the low enzyme activity of CHS. Alternatively, Gao et al (2019) introduced the SmCHS2 from Silybum marianum into Saccharomyces cerevisiae and obtained 648.63 mg/L naringenin by exogenously feeding p-coumaric acid.…”

Section: Flavanonesmentioning

confidence: 99%

Metabolic Engineering of Microorganisms for the Production of Flavonoids

Sheng

Sun

Yan

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Flavonoids are a class of secondary metabolites found in plant and fungus. They have been widely used in food, pharmaceutical, and nutraceutical industries owing to their significant biological activities, such as antiaging, antioxidant, anti-inflammatory, and anticancer. However, the traditional approaches for the production of flavonoids including chemical synthesis and plant extraction involved hazardous materials and complicated processes and also suffered from low product titer and yield. Microbial synthesis of flavonoids from renewable biomass such as glucose and xylose has been considered as a sustainable and environmentally friendly method for large-scale production of flavonoids. Recently, construction of microbial cell factories for efficient biosynthesis of flavonoids has gained much attention. In this article, we summarize the recent advances in microbial synthesis of flavonoids including flavanones, flavones, isoflavones, flavonols, flavanols, and anthocyanins. We put emphasis on developing pathway construction and optimization strategies to biosynthesize flavonoids and to improve their titer and yield. Then, we discuss the current challenges and future perspectives on successful strain development for large-scale production of flavonoids in an industrial level.

show abstract

“…Flavonoids represent one of the largest groups of natural products that widespread in the dietary fruits and vegetables 1–3. These polyphenols exhibit diverse physiological functions such as flower coloration, inhibition of pest growth, defense against pathogens, and UV protection 4–7.…”

Section: Introductionmentioning

confidence: 99%

FlavonoidC‐Glycosyltransferases: Function, Evolutionary Relationship, Catalytic Mechanism and Protein Engineering

Dai

Chen

et al. 2021

ChemBioEng Reviews

View full text Add to dashboard Cite

C‐glycosylflavonoids are polyphenolic phytochemicals that are ubiquitously distributed in the plant kingdom and confer a wealth of health‐promoting benefits to human body. These compounds harbor one or more sugar moieties that are attached to various regions of the flavonoid scaffold through rigid C–C glycosidic bonds. The diverse structures of C‐glycosylflavonoids are granted by the prominent reactions of flavonoid C‐glycosyltransferases (CGTs). This review gives an extensive overview of CGTs that are involved in the biosynthesis of C‐glycosylflavonoids, focusing on their evolutionary relationship and substrate specificity. Furthermore, structural insights into the catalytic mechanism and protein engineering of flavonoid CGTs are summarized. This review provides an important guidance for identification of novel flavonoid CGTs, biosynthesis of C‐glycosylflavonoids, and elucidation of the function‐structure relationship of flavonoid CGTs.

show abstract

Efficient Biosynthesis of (2S)-Naringenin from p-Coumaric Acid in Saccharomyces cerevisiae

Cited by 75 publications

References 53 publications

Comparative Molecular Mechanisms of Biosynthesis of Naringenin and Related Chalcones in Actinobacteria and Plants: Relevance for the Obtention of Potent Bioactive Metabolites

Comparative Molecular Mechanisms of Biosynthesis of Naringenin and Related Chalcones in Actinobacteria and Plants: Relevance for the Obtention of Potent Bioactive Metabolites

Metabolic Engineering of Microorganisms for the Production of Flavonoids

FlavonoidC‐Glycosyltransferases: Function, Evolutionary Relationship, Catalytic Mechanism and Protein Engineering

Contact Info

Product

Resources

About