Heterologous production of caffeic acid from tyrosine in Escherichia coli

Rodrigues, Joana Lúcia Lima Correia; Araújo, Rita; Prather, Kristala L. J.; Kluskens, Leon; Rodrigues, L. R.

doi:10.1016/j.enzmictec.2015.01.001

Cited by 73 publications

(82 citation statements)

References 33 publications

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“…This in turn impeded the evaluation of the impact of elevated substrate concentrations on microbial growth. However, cultivation experiments performed with substrate concentrations ranging from 0 and 2.5 m m revealed that the presence of 5‐bromoferulic acid ( 18 ) has a growth‐inhibiting effect similar to that of the naturally phenylpropenoic acids tested here and in other studies (Figure A) . With regard to the maximum achievable product titer in view of the cytotoxic effects of this compound for the cells, substrate concentrations between 2.5 and 3 m m turned out to most suitable, with up to 0.9 m m 5‐bromoferulic acid ( 18 ) being efficiently convertible into 5‐bromoconiferyl alcohol ( 19 , Figure B).…”

Section: Resultssupporting

confidence: 59%

“…Subsequently, the production of 5‐bromoconiferyl alcohol ( 19 ) with the aid of the engineered E. coli strain was optimized. Up to this point, substrate concentrations of 2.5 m m had been used in all biotransformations, because natural cinnamic acid derivatives are known to have an inhibitory effect on microbial growth . With the aim of balancing microbial growth and product yield, biotransformations with different 5‐bromoferulic acid ( 18 ) concentrations were performed in 48‐well microtiter plates in a microbioreactor system.…”

Section: Resultsmentioning

confidence: 99%

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Microbial Production of Natural and Unnatural Monolignols with Escherichia coli

et al. 2019

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Phenylpropanoids and phenylpropanoid‐derived plant polyphenols find numerous applications in the food and pharmaceutical industries. In recent years, several microbial platform organisms have been engineered towards producing such compounds. However, for the most part, microbial (poly)phenol production is inspired by nature, so naturally occurring compounds have predominantly been produced to date. Here we have taken advantage of the promiscuity of the enzymes involved in phenylpropanoid synthesis and exploited the versatility of an engineered Escherichia coli strain harboring a synthetic monolignol pathway to convert supplemented natural and unnatural phenylpropenoic acids into their corresponding monolignols. The performed biotransformations showed that this strain is able to catalyze the stepwise reduction of chemically interesting unnatural phenylpropenoic acids such as 3,4,5‐trimethoxycinnamic acid, 5‐bromoferulic acid, 2‐nitroferulic acid, and a “bicyclic” p‐coumaric acid derivative, in addition to six naturally occurring phenylpropenoic acids.

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Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Microbial Production of Natural and Unnatural Monolignols with Escherichia coli

et al. 2019

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“…In the combination that includes pRSFduet_COMT, the accumulation of coumaric acid was very high since the beginning of the fermentation (at 15 h was 1.95 mM), while in the cases where pACYCduet_COMT was present, the accumulation was not that high (at 15 h was 0.809-0.889 mM) (data not shown). This very high accumulation of the intermediate may be not beneficial to the production of ferulic acid since coumaric acid, and caffeic acid, are reported to be toxic to the cells at high concentrations (Watts et al, 2006;Furuya and Kino, 2013;Huang et al, 2013;Zhang and Stephanopoulos, 2013;Rodrigues et al, 2015a). Nevertheless, the highest ferulic acid concentration obtained from tyrosine was 889 µM (172.6 mg/L).…”

Section: Production Of Ferulic Acid From Tyrosine Using Different Commentioning

confidence: 96%

“…After studying the ferulic acid production from caffeic acid, plasmids carrying the COMT gene were combined with previously constructed plasmids carrying TAL and C3H genes (Rodrigues et al, 2015a) to further evaluate the production of ferulic acid from tyrosine (Figure 3). As previously reported (Kang et al, 2012;Rodrigues et al, 2015aRodrigues et al, ,b, 2017, coumaric acid accumulates in very high concentrations since the beginning of the fermentation while caffeic acid production is limited due to the C3H catalytic efficiency. Regarding ferulic acid productions, the plasmid combinations that included pAC_COMT led to very low concentrations of ferulic acid and consequently, a higher accumulation of caffeic acid in the culture medium was found.…”

Section: Production Of Ferulic Acid From Tyrosine Using Different Commentioning

confidence: 99%

A Combinatorial Approach to Optimize the Production of Curcuminoids From Tyrosine in Escherichia coli

Rodrigues

Gomes

Rodrigues

2020

Front. Bioeng. Biotechnol.

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Curcuminoids are well-known for their therapeutic properties. However, their extraction from natural sources is environmentally unfriendly, expensive and limited by seasonal variability, highlighting the need for alternative production processes. We propose an optimized artificial biosynthetic pathway to produce curcuminoids, including curcumin, in Escherichia coli. This pathway involves six enzymes, tyrosine ammonia lyase (TAL), 4-coumarate 3-hydroxylase (C3H), caffeic acid O-methyltransferase (COMT), 4-coumarate-CoA ligase (4CL), diketide-CoA synthase (DCS), and curcumin synthase (CURS1). Curcuminoids pathway was divided in two modules, the first module included TAL, C3H and COMT and the second one 4CL, DCS and CURS1. Optimizing the first module of the pathway, from tyrosine to ferulic acid, enabled obtaining the highest ferulic acid titer reported so far (1325.1 µM). Afterward, ferulic acid was used as substrate to optimize the second module of the pathway. We achieved the highest concentration of curcumin ever reported (1529.5 µM), corresponding to a 59.4% increase. Subsequently, curcumin and other curcuminoids were produced from tyrosine (using the whole pathway) in mono-culture. The production increased comparing to a previously reported pathway that used a caffeoyl-CoA O-methyltransferase enzyme (to convert caffeoyl-CoA to feruloyl-CoA) instead of COMT (to convert caffeic to ferulic acid). Additionally, the potential of a co-culture approach was evaluated to further improve curcuminoids production by reducing cells metabolic burden. We used one E. coli strain able to convert tyrosine to ferulic acid and another able to convert the hydroxycinnamic acids produced by the first one to curcuminoids. The co-culture strategies tested led to 6.6 times increase of total curcuminoids (125.8 µM) when compared to the mono-culture system. The curcuminoids production achieved in this study corresponds to a 6817% improvement. In addition, by using an inoculation ratio of 2:1, although total curcuminoids production decreased, curcumin production was enhanced and reached 43.2 µM, corresponding to an improvement of 160% comparing to mono-culture system. To our knowledge, these values correspond to the highest titers of curcuminoids obtained to date. These results demonstrate the enormous potential of modular co-culture engineering to produce curcumin, and other curcuminoids, from tyrosine.

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“…Hence it was proved that CYP199A2 shows higher catalytic activity during the conversion of p-coumaric acid into caffeic acid than 4-coumarate 3-hydroxylase. The study reveals the possibility of producing more complex plant molecules with beneficial health effects such as flavonoids and curcuminoids [48]. f. Sequential hydroxylation of a Cytochrome P450 dependant conversion during xiamycin pathway.…”

Section: Figurementioning

confidence: 98%

Cytochrome P450s: Blueprints for Potential Applications in Plants

Ahmad¹,

Li²,

Liu³

2018

J Plant Biochem Physiol

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Cytochrome P450s belong to a particular class of enzymes (Oxygenases) which are extensively distributed in all classes of organisms that attract the interest of scientists worldwide. It has been proved multi-functioned super gene family that sophisticates the biosynthesis of several endogenous molecules and metabolism of discrete pharmacologically important oxymolecules such as Antibiotics, essential secondary metabolites, fatty acid conjugates, signaling molecules, lipid degradation, hormones and many more. In this article, we briefly overviewed the heterogeneous role of the superfamily of Cytochrome P450 based on recent advances in molecular biology and genetic engineering. The inevitable role of Cytochrome P450s proteins in the biosynthesis of secondary metabolites likewise Hormones, Flavonoids, signaling molecules and other important pigments in plants such as anthocyanin, terpenoids and their pharmacological significance are specifically focused. We have predicted the distinctive metabolic networks and molecular characteristics of Safflower genome based on extensive transcriptome analysis from various developmental stages of floral tissues. The presence of repeated sequences, high copy number coding and noncoding RNA sequences and high expression level in the petals provide a gateway to enable the development of all-inclusive gene networks for economic and clinical features of Cytochrome P450 family. The implementation of metabolic engineering in floral pigments and alteration in their biosynthetic pathways can be exploited for a comprehensive understanding of several other pathways which invites new avenues for novel therapeutic blueprints and drug development.

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Heterologous production of caffeic acid from tyrosine in Escherichia coli

Cited by 73 publications

References 33 publications

Microbial Production of Natural and Unnatural Monolignols with Escherichia coli

Microbial Production of Natural and Unnatural Monolignols with Escherichia coli

A Combinatorial Approach to Optimize the Production of Curcuminoids From Tyrosine in Escherichia coli

Cytochrome P450s: Blueprints for Potential Applications in Plants

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