Metabolic engineering for microbial production of shikimic acid

Krämer, Marco; Bongaerts, Johannes; Bovenberg, Roel A. L.; Kremer, Susanne; Müller, Ulrike; Orf, Sonja; Wubbolts, Marcel; Raeven, Leon

doi:10.1016/j.ymben.2003.09.001

Cited by 196 publications

(139 citation statements)

References 26 publications

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“…Moreover, splitting the pathway at chorismate would require the first nine genes to be cloned into one plasmid, while splitting at shikimate required the cloning of only the first six genes into the first plasmid, which was easier and faster to accomplish. Additionally, shikimate is stable in liquid culture and is commercially valuable as a precursor for the synthesis of Tamiflu (19).…”

Section: Resultsmentioning

confidence: 99%

Modular Engineering of l -Tyrosine Production in Escherichia coli

Juminaga

Baidoo

Redding-Johanson

et al. 2012

Appl Environ Microbiol

247

203

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Efficient biosynthesis of L-tyrosine from glucose is necessary to make biological production economically viable. To this end, we designed and constructed a modular biosynthetic pathway for L-tyrosine production in E. coli MG1655 by encoding the enzymes for converting erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to L-tyrosine on two plasmids. Rational engineering to improve L-tyrosine production and to identify pathway bottlenecks was directed by targeted proteomics and metabolite profiling. The bottlenecks in the pathway were relieved by modifications in plasmid copy numbers, promoter strength, gene codon usage, and the placement of genes in operons. One major bottleneck was due to the bifunctional activities of quinate/ shikimate dehydrogenase (YdiB), which caused accumulation of the intermediates dehydroquinate (DHQ) and dehydroshikimate (DHS) and the side product quinate; this bottleneck was relieved by replacing YdiB with its paralog AroE, resulting in the production of over 700 mg/liter of shikimate. Another bottleneck in shikimate production, due to low expression of the dehydroquinate synthase (AroB), was alleviated by optimizing the first 15 codons of the gene. Shikimate conversion to L-tyrosine was improved by replacing the shikimate kinase AroK with its isozyme, AroL, which effectively consumed all intermediates formed in the first half of the pathway. Guided by the protein and metabolite measurements, the best producer, consisting of two medium-copy-number, dual-operon plasmids, was optimized to produce >2 g/liter L-tyrosine at 80% of the theoretical yield. This work demonstrates the utility of targeted proteomics and metabolite profiling in pathway construction and optimization, which should be applicable to other metabolic pathways.

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Section: Resultsmentioning

confidence: 99%

Modular Engineering of l -Tyrosine Production in Escherichia coli

Juminaga

Baidoo

Redding-Johanson

et al. 2012

Appl Environ Microbiol

247

203

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“…Shikimic acid is a precursor of oseltamivir phosphate which is the key ingredient in Tamiflu®. However, much of the shikimic acid manufactured are generated by an Escherichia coli that produces shikimic acid [49], [50], [51]. Liquidambar styraciflua were found to contain shikimic acid in the bark and seeds [52], [53] and can potentially produce commercial quantities.…”

Section: Discussionmentioning

confidence: 99%

Determination of allelopathic potentials in plant species in Sino-Japanese floristic region by sandwich method and dish pack method

Appiah

Zeng

et al. 2015

IJBAS

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The Sino-Japanese Floristic Region appears as one of the major centers of development of higher plants. This region have been relevant for the study of evolution and systematics of many flowering plants. The taxonomic richness of endemic plant species in this region have survived several years of extreme climate conditions. Endemic mountainous plant species that have survived extreme climate conditions are of allelopathic and medicinal interest. For this reason, 251 plant species collected from the Sino-Japanese Floristic Region were screened for allelopathic plant species. Sandwich method and dish pack method were respectively used to screen plant leaf leachates and volatile materials with lettuce (Lactuca sativa CV. Great Lakes 366) as receptor plant. Among the 84 species that showed inhibitory effect on lettuce radicle elongation in our sandwich bioassay, Photinia glabra showed complete inhibition of lettuce radicle elongation (0% radicle elongation). In the dish pack bioassay, Photinia glabra, Liquidambar styraciflua, and Cinnamomum camphora (90.6%, 61.4%, and 50.2% respectively) were among the nine species that were observed with strong inhibitory effect on lettuce radicle growth. On the other hand, nine other species promoted lettuce radicle growth when compared to the control. Aesculus turbinata and Quercus gilva were the species with the highest growth stimulatory effect (33.0% and 16.1% respectively). We hereby present Photinia glabra as an allelopathic candidate species for both leachate and volatile compounds.

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“…The main biologically active ingredients to have been determined to date were volatile and fatty oils, proteins, and resins. In 2005, Illicium verum biomass was used in the production of Tamiflu, and two independent reports appeared in the literature demonstrating that the key intermediate in the synthesis of Tamiflu (i.e., shikimic acid) could be extracted from Illicium verum (5,10). Unfortunately, however, the rich extractives of the Illicium verum biomass have traditionally been wasted because of inefficient extraction and separation processes.…”

Section: Introductionmentioning

confidence: 99%