Metabolic engineering of the E. coli l-phenylalanine pathway for the production of d-phenylglycine (d-Phg)

Müller, Ulrike; Assema, Friso van; Gunsior, Michele; Orf, Sonja; Kremer, Susanne; Schipper, Dick; Wagemans, A.H.A.; Townsend, Craig A.; Sonke, Theo; Bovenberg, Roel A. L.; Wubbolts, Marcel

doi:10.1016/j.ymben.2005.12.001

Cited by 60 publications

(69 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phg, as an aproteinogenic amino acid, is only found in streptogramin antibiotics such as virginiamycin. The enantiomeric isomer d-Phg plays an important role in the fine chemicals industry, where it is used as a precursor for the production of semisynthetic ␤-lactam antibiotics, such as cephalosporins and penicillins (Müller et al, 2006).…”

Section: Abbreviationsmentioning

confidence: 99%

Identification and functional characterization of phenylglycine biosynthetic genes involved in pristinamycin biosynthesis in Streptomyces pristinaespiralis

Mast

Wohlleben

Schinko

2011

Journal of Biotechnology

View full text Add to dashboard Cite

Section: Abbreviationsmentioning

confidence: 99%

Identification and functional characterization of phenylglycine biosynthetic genes involved in pristinamycin biosynthesis in Streptomyces pristinaespiralis

Mast

Wohlleben

Schinko

2011

Journal of Biotechnology

View full text Add to dashboard Cite

“…In order to elevate the carbon flux in the PPA synthetic pathway and thus effectively enhance the supply of precursor, overexpression of the feedback resistance of DAHP (3-deoxy- d -arabino-heptulosonate-7-phosphate) synthase ( aroF fbr ) and chorismate mutase/prephenate dehydratase ( pheA fbr ) are common strategies [24, 33]. The strains harboring the aroF fbr and pheA fbr expression plasmid pSUFAQ [24] in Sun21 and YL01 were YL02 and YL03, respectively (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…In previous reports, engineered PPA synthetic pathways have been expanded to obtain a lot of valuable products [24, 32, 33, 35]. In this study, the PPA pathway was engineered for enhanced IPA biosynthesis.…”

Section: Resultsmentioning

confidence: 99%

Metabolic engineering of indole pyruvic acid biosynthesis in Escherichia coli with tdiD

et al. 2017

View full text Add to dashboard Cite

BackgroundIndole pyruvic acid (IPA) is a versatile platform intermediate and building block for a number of high-value products in the pharmaceutical and food industries. It also has a wide range of applications, such as drugs for the nervous system, cosmetics, and luminophores. Chemical synthesis of IPA is a complicated and costly process. Moreover, through the biosynthesis route employing l-amino acid oxidase, the byproduct hydrogen peroxide leads the degradation of IPA. TdiD, identified as a specific tryptophan aminotransferase, could be an alternative solution for efficient IPA biosynthesis.Results Escherichia coli strain W3110, which demonstrates basic production when supplied with tryptophan, was engineered for IPA biosynthesis. Several strategies were implemented to improve IPA production. First, through incorporating the codon-optimized tdiD into W3110, IPA levels increased from 41.54 ± 1.26 to 52.54 ± 2.08 mg/L. Second, after verifying the benefit of an increased phenylpyruvate pool, a YL03 strain was constructed based on a previously reported mutant strain of W3110 with a plasmid carrying aroF fbr and pheA fbr to further improve IPA production. The recombinant YL03 strain accumulated IPA at 158.85 ± 5.36 mg/L, which was 3.82-fold higher than that of the wild-type W3110 strain. Third, optimization of tdiD co expression was carried out by replacing the Trc promoter with a series of constitutively active promoters along with increasing the plasmid copy numbers. The highest IPA production was observed in YL08, which achieved 236.42 ± 17.66 mg/L and represented a greater than 5-fold increase as compared to W3110. Finally, the effects of deletion and overexpression of tnaA on IPA biosynthesis were evaluated. The removal of tnaA led to slightly reduced IPA levels, whereas the overexpression of tnaA resulted in a considerable decline in production.ConclusionsThis study illustrates the feasibility of IPA biosynthesis in E. coli through tdiD. An efficient IPA producing strain, YL08, was developed, which provides a new possibility for biosynthesis of IPA. Although the final production was limited, this study demonstrates a convenient method of IPA synthesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-016-0620-6) contains supplementary material, which is available to authorized users.

show abstract

“…Another elegant early example of synthetic engineering of biosynthetic pathways is displayed in the work of Müller et al 101 , who engineered a pathway for the biosynthesis of d-hydroxyphenylglycine, an important building block for the side chain of semi-synthetic penicillins and cephalosporins. They combined a hydroxymandelate synthase and a hydroxymandelate oxidase from Streptomyces coelicolor and Amycolatopsis orientalis with a stereo-inverting hydroxyphenylglycine aminotransferase from Pseudomonas putida.…”

Section: Box 1 | Experimental Successes In Synthetic Pathway Engineeringmentioning

confidence: 99%

Computational tools for the synthetic design of biochemical pathways

et al. 2012

View full text Add to dashboard Cite

As the field of synthetic biology is developing, the prospects for de novo design of biosynthetic pathways are becoming more and more realistic. Hence, there is an increasing need for computational tools that can support these efforts. A range of algorithms has been developed that can be used to identify all possible metabolic pathways and their corresponding enzymatic parts. These can then be ranked according to various properties and modelled in an organism-specific context. Finally, design software can aid the biologist in the integration of a selected pathway into smartly regulated transcriptional units. Here, we review key existing tools and offer suggestions for how informatics can help to shape the future of synthetic microbiology.

show abstract

Metabolic engineering of the E. coli l-phenylalanine pathway for the production of d-phenylglycine (d-Phg)

Cited by 60 publications

References 24 publications

Identification and functional characterization of phenylglycine biosynthetic genes involved in pristinamycin biosynthesis in Streptomyces pristinaespiralis

Identification and functional characterization of phenylglycine biosynthetic genes involved in pristinamycin biosynthesis in Streptomyces pristinaespiralis

Metabolic engineering of indole pyruvic acid biosynthesis in Escherichia coli with tdiD

Computational tools for the synthetic design of biochemical pathways

Contact Info

Product

Resources

About