Rational engineering of the shikimate and related pathways in Corynebacterium glutamicum for 4-hydroxybenzoate production

Purwanto, Henry Syukur; Kang, Mi-Sook; Ferrer, Lenny; Han, Sangsoo; Lee, Jin Young; Kim, Kwang Ho; Lee, Jinho

doi:10.1016/j.jbiotec.2018.07.016

Cited by 35 publications

(35 citation statements)

References 34 publications

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“…Some examples from literature [ 199 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 214 , 217 , 218 , 221 , 224 , 225 , 226 , 227 , 228 , 231 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 ] of the highest production of phenolic acids biosynthesised by the engineered microorganisms are presented in Supplementary Materials Table S1 . However, there are no data on the production of other phenolic acids, such as isovanillic, o -vanillic ( 7 ), and isoferulic acids and isomers of p -coumaric, 6-methyl salicylic, and α-resorcyllic acids, by the engineered microorganisms.…”

Section: Production Of Phenolic Acids Using Non-modified and Enginmentioning

confidence: 99%

Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

et al. 2020

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Biotechnological production of phenolic acids is attracting increased interest due to their superior antioxidant activity, as well as other antimicrobial, dietary, and health benefits. As secondary metabolites, primarily found in plants and fungi, they are effective free radical scavengers due to the phenolic group available in their structure. Therefore, phenolic acids are widely utilised by pharmaceutical, food, cosmetic, and chemical industries. A demand for phenolic acids is mostly satisfied by utilising chemically synthesised compounds, with only a low quantity obtained from natural sources. As an alternative to chemical synthesis, environmentally friendly bio-based technologies are necessary for development in large-scale production. One of the most promising sustainable technologies is the utilisation of microbial cell factories for biosynthesis of phenolic acids. In this paper, we perform a systematic comparison of the best known natural sources of phenolic acids. The advances and prospects in the development of microbial cell factories for biosynthesis of these bioactive compounds are discussed in more detail. A special consideration is given to the modern production methods and analytics of phenolic acids.

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Section: Production Of Phenolic Acids Using Non-modified and Enginmentioning

confidence: 99%

Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

et al. 2020

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“…Two bottlenecks observed with the C. glutamicum strain engineered here may be overcome by future metabolic engineering: incomplete conversion of shikimate to anthranilate and incomplete N -methylation of anthranilate by SAM-dependent ANMT. To improve conversion of shikimate to anthranilate from about half to full conversion (compare about 1.4 g·L −1 of shikimate and 2.6 g·L −1 anthranilate produced by NMA105 in bioreactor cultivation; Figure 6 ), expression of the operon aroC KB encoding chorismate synthase, shikimate kinase, and 3-dehydroquinate synthase may be boosted, e.g., by changing the endogenous promoter for the strong promoter P tuf and using shikimate kinase from Methanocaldococcus jannaschii as shown previously [ 36 ]. In addition, various studies have shown that deletion of the chorismate mutase will increase the carbon flux towards tryptophan biosynthesis [ 36 , 40 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

“…In ARO04, the gene aroR, which codes for a translational regulatory leader peptide and is located upstream of DHAP synthase gene aroF [61], was replaced by an ilvC promoter followed by an optimized RBS in order to relieve negative translational control of aroF by phenylalanine and tyrosine. As described previously [36], the qsuABCD operon was replaced by qsuC transcribed from the constitutive strong tuf promoter in strain ARO05. This blocked conversion of 3-dehydroshikimate (3-DHS) to the unwanted by-product protocatechuate (PCA) on the one hand and increased the flux from 3-dehydroquinate (3-DHQ) to 3-DHS on the other hand.…”

Section: Construction Of a C Glutamicum Platform Strain For Productimentioning

confidence: 99%

“…A well-established toolbox enabled metabolic engineered-based approaches for production of diverse value-added compounds. Besides the production of proteinogenic amino acids, also a broad range of non-proteinogenic amino acid products like γ-aminobutyrate [ 29 ], 5-aminovalerate [ 30 , 31 ], pipecolic acid [ 32 , 33 ], N -methylated amino acids like N -methylalanine (NMeAla) [ 34 ] and sarcosine [ 35 ], aromatic compounds like 4-hydroxybenzoate [ 36 , 37 ] or protocatechuic acid [ 38 ], and functionalized aromatics like 7-chloro- or 7-bromo-tryptophan [ 39 , 40 ] and O -methylanthranilate [ 41 ] have been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Fermentative N-Methylanthranilate Production by Engineered Corynebacterium glutamicum

et al. 2020

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The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermentation processes using the Gram-positive bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the aromatic amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing by-product formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in production of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate production. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L−1 with a volumetric productivity of 0.01 g·L−1·h−1 and a yield of 4.8 mg·g−1 glucose.

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“…On the one hand, chorismate, which is formed via the shikimate pathway, can be converted into 4-hydroxybenzoate and pyruvate by the chorismate-pyruvate-lyase (EC 4.1.3.40, UbiC). This reaction was already exploited in Escherichia coli, Corynebacterium glutamicum, Klebsiella pneumoniae , and Pseudomonas putida KT2440 (Müller et al, 1995; Barker and Frost, 2001; Yu et al, 2016; Kallscheuer and Marienhagen, 2018; Kitade et al, 2018; Syukur Purwanto et al, 2018). However, in order to assure sufficient flux toward product formation, shutting down competing chorismate consuming pathways is often required.…”

Section: Introductionmentioning

confidence: 99%

High-Yield Production of 4-Hydroxybenzoate From Glucose or Glycerol by an Engineered Pseudomonas taiwanensis VLB120

Lenzen

Wynands

Otto

et al. 2019

Front. Bioeng. Biotechnol.

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Aromatic compounds such as 4-hydroxybenzoic acid are broadly applied in industry for a myriad of applications used in everyday life. However, their industrial production currently relies heavily on fossil resources and involves environmentally unfriendly production conditions, thus creating the need for more sustainable biotechnological alternatives. In this study, synthetic biology was applied to metabolically engineer Pseudomonas taiwanensis VLB120 to produce 4-hydroxybenzoate from glucose, xylose, or glycerol as sole carbon sources. Genes encoding a 4-hydroxybenzoate production pathway were integrated into the host genome and the flux toward the central precursor tyrosine was enhanced by overexpressing genes encoding key enzymes of the shikimate pathway. The flux toward tryptophan biosynthesis was decreased by introducing a P290S point mutation in the trpE gene, and degradation pathways for 4-hydroxybenzoate, 4-hydroxyphenylpyruvate and 3-dehydroshikimate were knocked out. The resulting production strains were tailored for the utilization of glucose and glycerol through the rational modification of central carbon metabolism. In batch cultivations with a completely mineral medium, the best strain produced 1.37 mM 4-hydroxybenzoate from xylose with a C-mol yield of 8% and 3.3 mM from glucose with a C-mol yield of 19.0%. Using glycerol as a sole carbon source, the C-mol yield increased to 29.6%. To our knowledge, this is the highest yield achieved by any species in a fully mineral medium. In all, the efficient conversion of bio-based substrates into 4-hydroxybenzoate by these deeply engineered P. taiwanensis strains brings the renewable production of aromatics one step closer.

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Rational engineering of the shikimate and related pathways in Corynebacterium glutamicum for 4-hydroxybenzoate production

Cited by 35 publications

References 34 publications

Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

Fermentative N-Methylanthranilate Production by Engineered Corynebacterium glutamicum

High-Yield Production of 4-Hydroxybenzoate From Glucose or Glycerol by an Engineered Pseudomonas taiwanensis VLB120

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