Production of p-hydroxycinnamic acid from glucose in Saccharomyces cerevisiae and Escherichia coli by expression of heterologous genes from plants and fungi

Vannelli, Todd; Qi, Wei; Sweigard, James A.; Gatenby, Anthony A.; Sariaslani, F. Sima

doi:10.1016/j.ymben.2006.11.001

Cited by 149 publications

(132 citation statements)

References 27 publications

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“…Several enzymes have previously been characterized both in vivo and in vitro, and the data are available from both patent and scientific literature (3,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). However, the conditions of kinetic analysis are often quite different and may not represent the extent to which the enzymes perform in vivo.…”

mentioning

confidence: 99%

Highly Active and Specific Tyrosine Ammonia-Lyases from Diverse Origins Enable Enhanced Production of Aromatic Compounds in Bacteria and Saccharomyces cerevisiae

Jendresen

Stahlhut

et al. 2015

Appl Environ Microbiol

164

183

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Phenylalanine and tyrosine ammonia-lyases form cinnamic acid and p-coumaric acid, which are precursors of a wide range of aromatic compounds of biotechnological interest. Lack of highly active and specific tyrosine ammonia-lyases has previously been a limitation in metabolic engineering approaches. We therefore identified 22 sequences in silico using synteny information and aiming for sequence divergence. We performed a comparative in vivo study, expressing the genes intracellularly in bacteria and yeast. When produced heterologously, some enzymes resulted in significantly higher production of p-coumaric acid in several different industrially important production organisms. Three novel enzymes were found to have activity exclusively for phenylalanine, including an enzyme from the low-GC Gram-positive bacterium Brevibacillus laterosporus, a bacterial-type enzyme from the amoeba Dictyostelium discoideum, and a phenylalanine ammonia-lyase from the moss Physcomitrella patens (producing 230 M cinnamic acid per unit of optical density at 600 nm [OD 600 ]) in the medium using Escherichia coli as the heterologous host). Novel tyrosine ammonia-lyases having higher reported substrate specificity than previously characterized enzymes were also identified. Enzymes from Herpetosiphon aurantiacus and Flavobacterium johnsoniae resulted in high production of p-coumaric acid in Escherichia coli (producing 440 M p-coumaric acid OD 600 unit ؊1 in the medium) and in Lactococcus lactis. The enzymes were also efficient in Saccharomyces cerevisiae, where p-coumaric acid accumulation was improved 5-fold over that in strains expressing previously characterized tyrosine ammonia-lyases. Small organic molecules of biotechnological interest include aromatic structures that are derived from p-coumaric acid (pHCA). pHCA can be formed from phenylalanine either through deamination to cinnamic acid (CA) by phenylalanine ammonialyase (PAL; EC 4.3.1.24) and subsequent hydroxylase activity by trans-cinnamate-4-monooxygenase or through deamination of tyrosine by tyrosine ammonia-lyase (TAL; EC 4.3.1.23) (Fig. 1). Considering that the route from phenylalanine requires activity of a P450 enzyme, which has been shown to be the limiting step in previous engineering strategies (1, 2), deamination of tyrosine for production of pHCA may be preferred in microbial cell factories. Tyrosine ammonia-lyases (TAL) have been employed for the production of plant biochemicals and aromatic compounds, e.g., for pHCA itself (3-5), or in the production of stilbenes, such as resveratrol (6, 7), flavonoids, such as naringenin (8, 9), cinnamoyl anthranilates (10), or plastic precursors, such as p-hydroxystyrene (11, 12), yet the TAL reaction may be the limiting step (10, 13).Due to the significant interest in production of phenolic compounds in biotechnological processes, we aimed at increasing the range of characterized phenylalanine ammonia-lyases (PAL) and tyrosine ammonia-lyases (TAL), and in particular at identifying the optimal TAL for use in microbial cell factories...

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mentioning

confidence: 99%

Highly Active and Specific Tyrosine Ammonia-Lyases from Diverse Origins Enable Enhanced Production of Aromatic Compounds in Bacteria and Saccharomyces cerevisiae

Jendresen

Stahlhut

et al. 2015

Appl Environ Microbiol

164

183

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“…When using a tyrosine-overproducing strain, 767 mg/liter caffeic acid was produced in 72 h using shake flasks. In this work, the authors used Rhodotorula glutinis TAL (RgTAL), which was reported to be the most active TAL among all the identified ones (150,(173)(174)(175) (Table 4). Zhang and Stephanopoulos (152) also used RgTAL for caffeic acid biosynthesis, in an experiment using two parallel routes and a tyrosine overproducer strain (Fig.…”

Section: Figmentioning

confidence: 99%

“…Other enzymes from the phenylpropanoid pathway, such as PAL from Rhodosporidium toruloides and a Populus hybrid, RsTAL, RcTAL, RgTAL, 4CL2 from Nicotiana tabacum, 4CL216 from a Populus hybrid, 4CL from G. max, Le4CL1, At4CL1, and Pc4CL2, were also successfully expressed in yeast (115,(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)174). The At4CL1 gene seems to be the best option to produce resveratrol in S. cerevisiae (139), since its yield was more than 65 times higher than when using 4CL216 from Populus hybrid (125) and 4CL2 from Nicotiana tabacum (124) in similar experiments using Vitis vinifera STS (stilbene synthase).…”

Section: Figmentioning

confidence: 99%

Heterologous Production of Curcuminoids

Rodrigues

Prather

Kluskens

et al. 2015

Microbiol Mol Biol Rev

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SUMMARY Curcuminoids, components of the rhizome of turmeric, show several beneficial biological activities, including anticarcinogenic, antioxidant, anti-inflammatory, and antitumor activities. Despite their numerous pharmaceutically important properties, the low natural abundance of curcuminoids represents a major drawback for their use as therapeutic agents. Therefore, they represent attractive targets for heterologous production and metabolic engineering. The understanding of biosynthesis of curcuminoids in turmeric made remarkable advances in the last decade, and as a result, several efforts to produce them in heterologous organisms have been reported. The artificial biosynthetic pathway (e.g., in Escherichia coli ) can start with the supplementation of the amino acid tyrosine or phenylalanine or of carboxylic acids and lead to the production of several natural curcuminoids. Unnatural carboxylic acids can also be supplemented as precursors and lead to the production of unnatural compounds with possibly novel therapeutic properties. In this paper, we review the natural conversion of curcuminoids in turmeric and their production by E. coli using an artificial biosynthetic pathway. We also explore the potential of other enzymes discovered recently or already used in other similar biosynthetic pathways, such as flavonoids and stilbenoids, to increase curcuminoid yield and activity.

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“…The production of valuable chemicals and pharmaceutically important natural products by microbial metabolic engineering is becoming an important component of industrial biotechnology. Thus, the CaC4H2-catalyzed regiospecific para-hydroxylation of trans-cinnamic acid to p-coumaric acid will be a useful candidate by using combinatorial biosynthesis approaches to create various plant phenylpropanoids (Kaneko et al 2003;Ro and Douglas 2004;Vannelli et al 2007). The present work will facilitate the investigations into the enzymes involved in the phenylpropanoid metabolism in C. acuminata and accelerate the rational design to produce various novel phenylpropanoids via the metabolic engineering approaches.…”

Section: Heterologous Overexpression and Catalytic Properties Of Cac4h2mentioning

confidence: 99%

Molecular cloning and functional characterization of a cinnamate 4-hydroxylase-encoding gene from Camptotheca acuminata

Yang

Jiang

et al. 2016

Acta Physiol Plant

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Cinnamate 4-hydroxylase (C4H) catalyzes the regioselective para-hydroxylation of trans-cinnamic acid to form p-coumaric acid, the biosynthetic precursor of phenylpropanoid-based polymers. These biopolymers play an essential role in plant structure construction, development, and defense. Herein the open reading frame of CaC4H2 was cloned from Camptotheca acuminata, a deciduous camptothecin-producing tree native to China. CaC4H2 showed 94 % amino acid residues identity with those of reported CaC4H, which suggested that CaC4H2 is an isoform of C4Hs presented in C. acuminata. The intact CaC4H2 was overexpressed in Escherichia coli with its functional reaction partner cytochrome P450 reductase, CamCPR, which transfers electrons from NADPH to CaC4H2 to support the catalytic hydroxylation activity of CaC4H2. Upon incubating trans-cinnamic acid with the recombinant CaC4H2 and tCamCPR, the formation of pcoumaric acid was confirmed by the HPLC-DAD and UPLC-DAD-ESIMS analyses, which indicated the catalytic hydroxylation activity of CaC4H2. Quantitative realtime PCR analyses showed that CaC4H2 was expressed in all tissues of C. acuminata seedlings, which is consistent with the well-known conclusion that the C4H-catalyzed hydroxylation reaction is a key step within the biosynthetic pathway of phenylpropanoids. The functional characterization of CaC4H2 will be useful for molecular breeding and sustainable utilization and protection of the camptothecin-producing plant.

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Production of p-hydroxycinnamic acid from glucose in Saccharomyces cerevisiae and Escherichia coli by expression of heterologous genes from plants and fungi

Cited by 149 publications

References 27 publications

Highly Active and Specific Tyrosine Ammonia-Lyases from Diverse Origins Enable Enhanced Production of Aromatic Compounds in Bacteria and Saccharomyces cerevisiae

Highly Active and Specific Tyrosine Ammonia-Lyases from Diverse Origins Enable Enhanced Production of Aromatic Compounds in Bacteria and Saccharomyces cerevisiae

Heterologous Production of Curcuminoids

Molecular cloning and functional characterization of a cinnamate 4-hydroxylase-encoding gene from Camptotheca acuminata

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