Production of three phenylethanoids, tyrosol, hydroxytyrosol, and salidroside, using plant genes expressing in Escherichia coli

Chung, Daeun; Kim, So Yeon; Ahn, Joong‐Hoon

doi:10.1038/s41598-017-02042-2

Cited by 98 publications

(84 citation statements)

References 39 publications

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“…The resulting strain did not synthesize detectable levels of avn F, but anthranilate and caffeic acid were found in the culture filtrate. A similar phenomenon was previously observed for the synthesis of hydroxysalidroside, in which the introduction of one additional gene in the stepwise synthesis interfered with the whole reaction, resulting in no product formation [35]. Another possible explanation is that HCBT used caffeic acid less effectively than p -coumaric acid (Table 3), while the attachment of CoA into either p -coumaric acid or caffeic by 4CL was similar [36].…”

Section: Resultssupporting

confidence: 67%

Synthesis of avenanthramides using engineered Escherichia coli

et al. 2018

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BackgroundHydroxycinnamoyl anthranilates, also known as avenanthramides (avns), are a group of phenolic alkaloids with anti-inflammatory, antioxidant, anti-itch, anti-irritant, and antiatherogenic activities. Some avenanthramides (avn A–H and avn K) are conjugates of hydroxycinnamic acids (HC), including p-coumaric acid, caffeic acid, and ferulic acid, and anthranilate derivatives, including anthranilate, 4-hydroxyanthranilate, and 5-hydroxyanthranilate. Avns are primarily found in oat grain, in which they were originally designated as phytoalexins. Knowledge of the avns biosynthesis pathway has now made it possible to synthesize avns through a genetic engineering strategy, which would help to further elucidate their properties and exploit their beneficial biological activities. The aim of the present study was to synthesize natural avns in Escherichia coli to serve as a valuable resource.ResultsWe synthesized nine avns in E. coli. We first synthesized avn D from glucose in E. coli harboring tyrosine ammonia lyase (TAL), 4-coumarate:coenzyme A ligase (4CL), anthranilate N-hydroxycinnamoyl/benzoyltransferase (HCBT), and anthranilate synthase (trpEG). A trpD deletion mutant was used to increase the amount of anthranilate in E. coli. After optimizing the incubation temperature and cell density, approximately 317.2 mg/L of avn D was synthesized. Avn E and avn F were then synthesized from avn D, using either E. coli harboring HpaBC and SOMT9 or E. coli harboring HapBC alone, respectively. Avn A and avn G were synthesized by feeding 5-hydroxyanthranilate or 4-hydroxyanthranilate to E. coli harboring TAL, 4CL, and HCBT. Avn B, avn C, avn H, and avn K were synthesized from avn A or avn G, using the same approach employed for the synthesis of avn E and avn F from avn D.ConclusionsUsing different HCs, nine avns were synthesized, three of which (avn D, avn E, and avn F) were synthesized from glucose in E. coli. These diverse avns provide a strategy to synthesize both natural and unnatural avns, setting a foundation for exploring the biological activities of diverse avns.Electronic supplementary materialThe online version of this article (10.1186/s12934-018-0896-9) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 67%

Synthesis of avenanthramides using engineered Escherichia coli

et al. 2018

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“…With the glycosyltransferase OsUGT13 from rice we here identified an alternative UGT, which was more suitable for glycosylation of tyrosol both in S. cerevisiae and C. glutamicum. Recently, and after we had finished our screening of UGTs, another salidroside pathway was reconstituted in E. coli, using a combination of various plant genes (Chung et al, 2017). In this study, UGT85A1 from Arabidopsis (Arabidopsis thaliana), which showed essentially full conversion of tyrosol to salidroside, allowed for product titers of up to 0.97 mM (290 mg L 21 ) after 48 h of cultivation.…”

Section: Discussionmentioning

confidence: 95%

Identification and Microbial Production of the Raspberry Phenol Salidroside that Is Active against Huntington’s Disease

et al. 2018

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Edible berries are considered to be among nature's treasure chests as they contain a large number of (poly)phenols with potentially health-promoting properties. However, as berries contain complex (poly)phenol mixtures, it is challenging to associate any interesting pharmacological activity with a single compound. Thus, identification of pharmacologically interesting phenols requires systematic analyses of berry extracts. Here, raspberry (Rubus idaeus, var Prestige) extracts were systematically analyzed to identify bioactive compounds against pathological processes of neurodegenerative diseases. Berry extracts were tested on different Saccharomyces cerevisiae strains expressing disease proteins associated with Alzheimer's, Parkinson's, or Huntington's disease, or amyotrophic lateral sclerosis. After identifying bioactivity against Huntington's disease, the extract was fractionated and the obtained fractions were tested in the yeast model, which revealed that salidroside, a glycosylated phenol, displayed significant bioactivity. Subsequently, a metabolic route to salidroside was reconstructed in S. cerevisiae and Corynebacterium glutamicum. The best-performing S. cerevisiae strain was capable of producing 2.1 mM (640 mg L 21 ) salidroside from Glc in shake flasks, whereas an engineered C. glutamicum strain could efficiently convert the precursor tyrosol to salidroside, accumulating up to 32 mM (9,700 mg L 21 ) salidroside in bioreactor cultivations (yield: 0.81 mol mol 21 ). Targeted yeast assays verified that salidroside produced by both organisms has the same positive effects as salidroside of natural origin.

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“…In another study, Aro8 and Aro10 from S. cerevisiae were overexpressed in E. coli and pheA and feaB were deleted, resulting in the synthesis of 4.15 mM tyrosol upon supplying 10 mM tyrosine [43]. By introducing the bifunctional gene AAS into E. coli and engineering the E. coli tyrosine biosynthesis pathway to increase intracellular tyrosine concentration by deleting tyrR and pheA, 3.77 mM tyrosol was synthesized [44]. When more genes (tyrA, ppsA, tktA, aroD, and aroB) of the shikimate pathway of E. coli (Fig.…”

Section: Phenylethanoid Synthesis In Microorganismsmentioning

confidence: 99%

“…The UGTs found so far attach glucose to both the phenolic hydroxyl group and alcoholic hydroxyl group. Chung et al [44] screened Arabidopsis thaliana UGTs to synthesize salidroside from tyrosol and found that AtUGT73C5, AtUGT73C6, and AtUGT85A1 specifically synthesized salidroside, and that AtUGT84A1 showed the highest production of salidroside. AtUGT84A1 also converted hydroxytyrosol into salidroside [49].…”

Section: Phenylethanoid Synthesis In Microorganismsmentioning

confidence: 99%

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Current Status of Microbial Phenylethanoid Biosynthesis

Kim¹,

Song²,

Jeon³

et al. 2018

Journal of Microbiology and Biotechnology

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Plants synthesize a variety of phenolic compounds via the phenylpropanoid pathway, which is a pathway unique to plants [1]. These phenolic compounds found in nature can be classified based on the backbone of their carbon skeleton (Table 1). Phenolic acid, whose carbon skeleton is benzoic acid derivatives (C6-C1), phenylethanoid (C6-C2), phenylpropanoid (C6-C3), stilbene (C6-C2-C6), and flavonoid (C6-C3-C6) are major groups [2]. Diverse phenolic compounds are being widely used in our current life. Some of them are building blocks for polymer synthesis [3], some are used as ingredients in food

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Production of three phenylethanoids, tyrosol, hydroxytyrosol, and salidroside, using plant genes expressing in Escherichia coli

Cited by 98 publications

References 39 publications

Synthesis of avenanthramides using engineered Escherichia coli

Synthesis of avenanthramides using engineered Escherichia coli

Identification and Microbial Production of the Raspberry Phenol Salidroside that Is Active against Huntington’s Disease

Current Status of Microbial Phenylethanoid Biosynthesis

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