Microbial production of natural raspberry ketone

Beekwilder, Jules; Meer, I.M. van der; Sibbesen, Ole; Broekgaarden, Mans; Qvist, I.; Mikkelsen, J.D.; Hall, Robert D.

doi:10.1002/biot.200700076

Cited by 86 publications

(106 citation statements)

References 24 publications

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“…Our success in fermentative production of flavonoids, stilbenoids and curcuminoids from the primary metabolites, phenylalanine and tyrosine, by E. coli by means of expressing artificially designed biosynthetic pathways makes this concept feasible. Examples are production of naringenin, eriodictyol, kaempferol and a few other compounds by p-coumaric acid-supplemented E. coli [76] and production of a raspberry ketone by E. coli [8]. This concept can be applied to production of many other compound classes by similar techniques, hopefully to paclitaxel and artemisnin as terpenoids and morphine, vincristine, and vinblastine as alkaloids.…”

Section: Discussionmentioning

confidence: 99%

“…Our success in fermentative production of plant-specific polyketides by E. coli carrying an artificially assembled phenylpropanoid pathway was the first example to show that a nearly complete biosynthetic pathway in plants was established in a heterologous microorganism for production of flavanones from the amino acid precursors, phenylalanine and tyrosine [5,6]. Later, Yan et al [7] produced 5-deoxyflavanones in E. coli and Beekwilder et al [8] produced a natural raspberry ketone in E. coli. The approach of this type of combining genes from different organisms and designing a gene cluster to produce a bioactive compound leads not only to diversification of both chemical and natural product libraries but also to efficient use of the potential of the host organisms, particularly when microorganisms are used as the hosts.…”

Section: Introductionmentioning

confidence: 99%

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Combinatorial Biosynthesis of Non-bacterial and Unnatural Flavonoids, Stilbenoids and Curcuminoids by Microorganisms

Horinouchi

2008

J Antibiot

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One of the approaches of combinatorial biosynthesis is combining genes from different organisms and designing a new set of gene clusters to produce bioactive compounds, leading to diversification of both chemical and natural product libraries. This makes efficient use of the potential of the host organisms, especially when microorganisms are used. An Escherichia coli system, in which artificial biosynthetic pathways for production of plant-specific medicinal polyketides, such as flavonoids, stilbenoids, isoflavonoids, and curcuminoids, are assembled, has been designed and expressed. Starting with amino acids tyrosine and phenylalanine as substrates, this system yields naringenin, resveratrol, genistein, and curcumin, for example, all of which are beneficial to human health because of their wide variety of biological activities. Supplementation of unnatural carboxylic acids to the recombinant E. coli cells carrying the artificial pathways by precursor-directed biosynthesis results in production of unnatural compounds. Addition of decorating or modification enzymes to the artificial pathway leads to production of natural and unnatural flavonols, flavones, and methylated resveratrols. This microbial system is promising for construction of larger libraries by employing other polyketide synthases and decorating enzymes of various origins. In addition, the concept of building and expressing artificial biosynthetic pathways for production of non-bacterial and unnatural compounds in microorganisms should be successfully applied to production of not only plant-specific polyketides but also many other useful compound classes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combinatorial Biosynthesis of Non-bacterial and Unnatural Flavonoids, Stilbenoids and Curcuminoids by Microorganisms

Horinouchi

2008

J Antibiot

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“…[89] However, the high cost of p-coumaric acid as a substrate and the trace amounts of this phenylpropanoid obtained in the previous iteration of a bioengineered yeast strain, did not offer a profitable option for commercial production of raspberry ketone. The recent de novo production of raspberry ketone in a haploid wine strain (AWRI1631) of S. cerevisiae was achieved via metabolic pathway engineering and synthetic enzyme fusion.…”

Section: Bioengineered Yeast Put Synthetic Dna To Work In Industrymentioning

confidence: 99%

Synthetic genome engineering forging new frontiers for wine yeast

Pretorius

2016

Critical Reviews in Biotechnology

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Over the past 15 years, the seismic shifts caused by the convergence of biomolecular, chemical, physical, mathematical, and computational sciences alongside cutting-edge developments in information technology and engineering have erupted into a new field of scientific endeavor dubbed Synthetic Biology. Recent rapid advances in high-throughput DNA sequencing and DNA synthesis techniques are enabling the design and construction of new biological parts (genes), devices (gene networks) and modules (biosynthetic pathways), and the redesign of biological systems (cells and organisms) for useful purposes. In 2014, the budding yeast Saccharomyces cerevisiae became the first eukaryotic cell to be equipped with a fully functional synthetic chromosome. This was achieved following the synthesis of the first viral (poliovirus in 2002 and bacteriophage Phi-X174 in 2003) and bacterial (Mycoplasma genitalium in 2008 and Mycoplasma mycoides in 2010) genomes, and less than two decades after revealing the full genome sequence of a laboratory (S288c in 1996) and wine (AWRI1631 in 2008) yeast strain. A large international project -the Synthetic Yeast Genome (Sc2.0) Project -is now underway to synthesize all 16 chromosomes ($12 Mb carrying $6000 genes) of the sequenced S288c laboratory strain by 2018. If successful, S. cerevisiae will become the first eukaryote to cross the horizon of in silico design of complex cells through de novo synthesis, reshuffling, and editing of genomes. In the meantime, yeasts are being used as cell factories for the semi-synthetic production of high-value compounds, such as the potent antimalarial artemisinin, and food ingredients, such as resveratrol, vanillin, stevia, nootkatone, and saffron. As a continuum of previously genetically engineered industrially important yeast strains, precision genome engineering is bound to also impact the study and development of wine yeast strains supercharged with synthetic DNA. The first taste of what the future holds is the de novo production of the raspberry ketone aroma compound, 4-[4-hydroxyphenyl]butan-2-one, in a wine yeast strain (AWRI1631), which was recently achieved via metabolic pathway engineering and synthetic enzyme fusion. A peek over the horizon is revealing that the future of "Wine Yeast 2.0" is already here. Therefore, this article seeks to help prepare the wine industry -an industry rich in history and tradition on the one hand, and innovation on the other -for the inevitable intersection of the ancient art practiced by winemakers and the inventive science of pioneering "synthetic genomicists". It would be prudent to proactively engage all stakeholders -researchers, industry practitioners, policymakers, regulators, commentators, and consumers -in a meaningful dialog about the potential challenges and opportunities emanating from Synthetic Biology. To capitalize on the new vistas of synthetic yeast genomics, this paper presents wine yeast research in a fresh context, raises important questions and proposes new directions. ARTICLE HISTORY

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“…Raspberry ketone was produced in E. coli and S. cerevisiae cells, in the former by introducing tobacco 4CL and raspberry CHS and incubating the cells with 3 mM 4-coumaric acid (Beekwilder et al 2007). Because of the endogenous reductase activity of E. coli, these cells produced naringenin as well as 4-hydroxybenzalacetone and raspberry ketone, suggesting that raspberry CHS has both CHS and BAS activity.…”

Section: Phenylbutanoidsmentioning

confidence: 99%

Microbial production of plant specialized metabolites

Suzuki

Koeduka

Sugiyama

et al. 2014

Plant Biotechnology

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Plant specialized metabolites play important roles in human life. These metabolites, however, are often produced in small amounts in particular plant species. Moreover, some of these species are endangered in their natural habitats, thus further limiting the availability of some plant specialized metabolites. Microbial production of these compounds may circumvent this problem. Considerable progress has been made in the microbial production of various plant specialized metabolites over the past decade. Now, the microbial production of these compounds is becoming robust, fine-tuned, and commercially relevant systems using the methods of synthetic biology. This review describes the progress of microbial production of plant specialized metabolites, including phenylpropanoids, flavonoids, stilbenoids, diarylheptanoids, phenylbutanoids, terpenoids, and alkaloids, and discusses future challenges in this field.

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Microbial production of natural raspberry ketone

Cited by 86 publications

References 24 publications

Combinatorial Biosynthesis of Non-bacterial and Unnatural Flavonoids, Stilbenoids and Curcuminoids by Microorganisms

Combinatorial Biosynthesis of Non-bacterial and Unnatural Flavonoids, Stilbenoids and Curcuminoids by Microorganisms

Synthetic genome engineering forging new frontiers for wine yeast

Microbial production of plant specialized metabolites

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