De novo biosynthesis of antimycobacterial agent geranylgeranyl acetate from glucose

Liu, Zhijie; Zong, Zhen; Chen, Zhuojing; Xu, Qian; Shi, Yong; Li, Dongsheng; Pan, Hong; Guo, Daoyi

doi:10.1016/j.bej.2018.11.008

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…In order to improve the biosynthesis of tyrosol acetate, strain needs to strengthen the activity of alcohol acetyltransferase. Alcohol acetyltransferase ATF1 from S. cerevisiae has been used for acetylation of a variety of alcohol [18][19][20][21]. Therefore, we speculated that the observed promiscuity of the ATF1 can extend also to tyrosol.…”

Section: Production Tyrosol Acetate From Glucosementioning

confidence: 99%

De novo biosynthesis of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered Escherichia coli

Guo

Sun

et al. 2021

Enzyme and Microbial Technology

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Background: Tyrosol and hydroxytyrosol derived from virgin olive oil and olives extract, have wide applications both as functional food components and as nutraceuticals. However, they have low bioavailability due to their low absorption and high metabolism in human liver and small intestine.Acetylation of tyrosol and hydroxytyrosol can effectively improve their bioavailability and thus increase their potential use in the food and cosmeceutical industries. There is no report on the bioproductin of tyrosol acetate and hydroxytyrosol acetate so far. Thus, it is of great signi cance to develop microbial cell factories for achieving tyrosol acetate or hydroxytyrosol acetate biosynthesis.Results: In this study, two de novo biosynthetic pathways for the production of tyrosol acetate and hydroxytyrosol acetate were constructed in Escherichia coli. First, an engineered E. coli that allows production of tyrosol from simple carbon sources was established. Four aldehyde reductases were compared, and it was found that yeaE is the best aldehyde reductase for tyrosol accumulation. Subsequently, the pathway was extended for tyrosol acetate production by further overexpression of alcohol acetyltransferase ATF1 for the conversion of tyrosol to tyrosol acetate. Finally, the pathway was further extended for hydroxytyrosol acetate production by overexpression of 4-hydroxyphenylacetate 3hydroxylase HpaBC. Conclusion:We have successfully established the arti cial biosynthetic pathway of tyrosol acetate and hydroxytyrosol acetate from fermentable sugars and demonstrated for the rst time the direct fermentative production of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered E. coli

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Section: Production Tyrosol Acetate From Glucosementioning

confidence: 99%

De novo biosynthesis of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered Escherichia coli

Guo

Sun

et al. 2021

Enzyme and Microbial Technology

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Section: Production Tyrosol Acetate From Glucosementioning

confidence: 99%

De novo Biosynthesis of Tyrosol Acetate and Hydroxytyrosol Acetate from Glucose in Engineered Escherichia Coli

Guo

Xiao

Sun

et al. 2021

Preprint

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Background: Tyrosol and hydroxytyrosol derived from virgin olive oil and olives extract, have wide applications both as functional food components and as nutraceuticals. However, they have low bioavailability due to their low absorption and high metabolism in human liver and small intestine. Acetylation of tyrosol and hydroxytyrosol can effectively improve their bioavailability and thus increase their potential use in the food and cosmeceutical industries. There is no report on the bioproductin of tyrosol acetate and hydroxytyrosol acetate so far. Thus, it is of great significance to develop microbial cell factories for achieving tyrosol acetate or hydroxytyrosol acetate biosynthesis.Results: In this study, two de novo biosynthetic pathways for the production of tyrosol acetate and hydroxytyrosol acetate were constructed in Escherichia coli. First, an engineered E. coli that allows production of tyrosol from simple carbon sources was established. Four aldehyde reductases were compared, and it was found that yeaE is the best aldehyde reductase for tyrosol accumulation. Subsequently, the pathway was extended for tyrosol acetate production by further overexpression of alcohol acetyltransferase ATF1 for the conversion of tyrosol to tyrosol acetate. Finally, the pathway was further extended for hydroxytyrosol acetate production by overexpression of 4-hydroxyphenylacetate 3-hydroxylase HpaBC.Conclusion: We have successfully established the artificial biosynthetic pathway of tyrosol acetate and hydroxytyrosol acetate from fermentable sugars and demonstrated for the first time the direct fermentative production of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered E. coli

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“…This reaction uses an alcohol acyltransferase (AAT) to generate an ester by condensing an alcohol and an acyl-CoA. AAT can catalyze a broad substrate range including (i) linear or branched short-to-long chain fatty alcohols [10, 11, 17], (ii) aromatic alcohols [18], and (iii) terpenols [19–22] as well as various fatty acyl-CoAs [11, 13]. To date, while microbial biosynthesis of the precursor metabolites for lactate esters have been well established such as lactate [13, 16, 23–27], lactyl-CoA [28–30], ethanol [31, 32], propanol [33], isopropanol [34], butanol [35], isobutanol [36], amyl alcohol [37], isoamyl alcohol [38], benzyl alcohol [39], 2-phenylethanol [40, 41], and terpenols [19–22], the direct microbial biosynthesis of lactate esters from fermentable sugars has not yet been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Microbial biosynthesis of lactate esters

Lee

Trinh

2019

Biotechnol Biofuels

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Background Green organic solvents such as lactate esters have broad industrial applications and favorable environmental profiles. Thus, manufacturing and use of these biodegradable solvents from renewable feedstocks help benefit the environment. However, to date, the direct microbial biosynthesis of lactate esters from fermentable sugars has not yet been demonstrated. Results In this study, we present a microbial conversion platform for direct biosynthesis of lactate esters from fermentable sugars. First, we designed a pyruvate-to-lactate ester module, consisting of a lactate dehydrogenase (ldhA) to convert pyruvate to lactate, a propionate CoA-transferase (pct) to convert lactate to lactyl-CoA, and an alcohol acyltransferase (AAT) to condense lactyl-CoA and alcohol(s) to make lactate ester(s). By generating a library of five pyruvate-to-lactate ester modules with divergent AATs, we screened for the best module(s) capable of producing a wide range of linear, branched, and aromatic lactate esters with an external alcohol supply. By co-introducing a pyruvate-to-lactate ester module and an alcohol (i.e., ethanol, isobutanol) module into a modular Escherichia coli (chassis) cell, we demonstrated for the first time the microbial biosynthesis of ethyl and isobutyl lactate esters directly from glucose. In an attempt to enhance ethyl lactate production as a proof-of-study, we re-modularized the pathway into (1) the upstream module to generate the ethanol and lactate precursors and (2) the downstream module to generate lactyl-CoA and condense it with ethanol to produce the target ethyl lactate. By manipulating the metabolic fluxes of the upstream and downstream modules through plasmid copy numbers, promoters, ribosome binding sites, and environmental perturbation, we were able to probe and alleviate the metabolic bottlenecks by improving ethyl lactate production by 4.96-fold. We found that AAT is the most rate-limiting step in biosynthesis of lactate esters likely due to its low activity and specificity toward the non-natural substrate lactyl-CoA and alcohols. Conclusions We have successfully established the biosynthesis pathway of lactate esters from fermentable sugars and demonstrated for the first time the direct fermentative production of lactate esters from glucose using an E. coli modular cell. This study defines a cornerstone for the microbial production of lactate esters as green solvents from renewable resources with novel industrial applications.

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De novo biosynthesis of antimycobacterial agent geranylgeranyl acetate from glucose

Cited by 7 publications

References 27 publications

De novo biosynthesis of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered Escherichia coli

De novo biosynthesis of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered Escherichia coli

De novo Biosynthesis of Tyrosol Acetate and Hydroxytyrosol Acetate from Glucose in Engineered Escherichia Coli

Microbial biosynthesis of lactate esters

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