Synthesis of Branched‐Chain Sugars with a DHAP‐Dependent Aldolase: Ketones are Electrophile Substrates of Rhamnulose‐1‐phosphate Aldolases

Laurent, Victor; Darii, Ekaterina; Aujon, Angelina; Debacker, M.; Petit, Jean‐Louis; Hélaine, Virgil; Liptaj, Tibor; Breza, Martin; Mariage, Aline; Nauton, Lionel; Traı̈kia, Mounir; Salanoubat, Marcel; Lemaire, Marielle; Guérard-Hélaine, Christine; Berardinis, Véronique de

doi:10.1002/anie.201712851

Cited by 23 publications

(31 citation statements)

References 49 publications

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“…Well-known members of this class include FucA, RhaD, fructose 1,6-diphosphate aldolase (FruA), and tagatose 1,6-diphosphate aldolase (TagA). To date, only one kind of DHAP-dependent aldolases has been discovered in catalyzing the aldol reaction between DHAP and ketones and in synthesizing branched-chain sugars [ 12 ]. To investigate whether other kinds of DHAP-dependent aldolases showed this catalytic property, RhaD, FucA, TagA and FruA from Escherichia coli were used as candidates to catalyze the aldol reaction between DHAP and DHA.…”

Section: Resultsmentioning

confidence: 99%

“…The other one is l -rhamnulose-1-phosphate aldolase (RhaD) from Bacteroides thetaiotaomicron . This enzyme catalyzes the aldol reaction between DHAP and several ketones (hydroxyacetone, 1-hydroxybutanone, hydroxypyruvate and l -erythrulose) and gave four branched-chain sugars by coupling an acid phosphatase [ 12 ]. The development of several kinds of aldolases that can tolerate ketones as electrophilic receptors is necessary in the asymmetric catalysis field.…”

Section: Introductionmentioning

confidence: 99%

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Biosynthesis of dendroketose from different carbon sources using in vitro and in vivo metabolic engineering strategies

Yang

Zhu

et al. 2018

Biotechnol Biofuels

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BackgroundAsymmetric aldol-type C–C bond formation with ketones used as electrophilic receptor remains a challenging reaction for aldolases as biocatalysts. To date, only one kind of dihydroxyacetone phosphate (DHAP)-dependent aldolases has been discovered and applied to synthesize branched-chain sugars directly using DHAP and dihydroxyacetone (DHA) as substrate. However, the unstable and high-cost properties of DHAP limit large-scale application. Therefore, biosynthesis of branched-chain sugar from low-cost and abundant carbon sources is essential.ResultsThe detailed catalytic property of l-rhamnulose-1-phosphate aldolase (RhaD) and l-fuculose-1-phosphate aldolase (FucA) from Escherichia coli in catalyzing the aldol reactions with DHA as electrophilic receptors was characterized. Furthermore, we calculated the Bürgi–Dunitz trajectory using molecular dynamics simulations, thereby revealing the original sources of the catalytic efficiency of RhaD and FucA. A multi-enzyme reaction system composed of formolase, DHA kinase, RhaD, fructose-1-phosphatase, and polyphosphate kinase was constructed to in vitro produce dendroketose, a branched-chain sugar, from one-carbon formaldehyde. The conversion rate reached 86% through employing a one-pot, two-stage reaction process. Moreover, we constructed two artificial pathways in Corynebacterium glutamicum to obtain this product in vivo starting from glucose or glycerol. Fermentation with glycerol as feedstock produced 6.4 g/L dendroketose with a yield of 0.45 mol/mol glycerol, representing 90% of the maximum theoretical value. Additionally, the dendroketose production reached 36.3 g/L with a yield of 0.46 mol/mol glucose when glucose served as the sole carbon resource.ConclusionsThe detailed enzyme kinetics data of the two DHAP-dependent aldolases with DHA as electrophilic receptors were presented in this study. In addition, insights into this catalytic property were given via in silico simulations. Moreover, the cost-effective synthesis of dendroketose starting from one-, three-, and six-carbon resources was achieved through in vivo and in vitro metabolic engineering strategies. This rare branched-chain ketohexose may serve as precursor to prepare 4-hydroxymethylfurfural and branched-chain alkanes using chemical method.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1293-7) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biosynthesis of dendroketose from different carbon sources using in vitro and in vivo metabolic engineering strategies

Yang

Zhu

et al. 2018

Biotechnol Biofuels

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“…, dark blue broken line arrows, followed by light green lines for the strictly anaerobic section). There, MTRu‐1‐P is first cleaved into dihydroxyacetone phosphate (DHAP) and 2‐(methylthio)acetaldehyde (North et al ., ), using a class II aldolase‐like protein that belongs to a family of promiscuous DHAP‐dependent enzymes widely spread in bacteria (Laurent et al ., ). A similar pathway may exist in other bacteria as well, but this has not been explored yet.…”

Section: Alternate Fates Of Mtru‐1‐p and Its By‐productsmentioning

confidence: 97%

Revisiting the methionine salvage pathway and its paralogues

Sekowska

Ashida

Danchin

2018

Microbial Biotechnology

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SummaryMethionine is essential for life. Its chemistry makes it fragile in the presence of oxygen. Aerobic living organisms have selected a salvage pathway (the MSP) that uses dioxygen to regenerate methionine, associated to a ratchet‐like step that prevents methionine back degradation. Here, we describe the variation on this theme, developed across the tree of life. Oxygen appeared long after life had developed on Earth. The canonical MSP evolved from ancestors that used both predecessors of ribulose bisphosphate carboxylase oxygenase (RuBisCO) and methanethiol in intermediate steps. We document how these likely promiscuous pathways were also used to metabolize the omnipresent by‐products of S‐adenosylmethionine radical enzymes as well as the aromatic and isoprene skeleton of quinone electron acceptors.

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“…In the course of a screening for new dihydroxyacetone (DHA)‐dependent aldolases, the unpredictable formation of dendroketose‐1‐phosphate catalyzed by a DHAP‐dependent Rhamnulose‐1‐phosphate (RhuA) aldolase C2JUR4 from Lactobacillus rhamnosus was detected . This non‐natural branched‐chain sugar generated from the cross‐aldol reaction between DHAP and DHA highlighted the ability of RhuA to use ketones as electrophilic partners of DHAP.…”

Section: Cross‐aldol Additionsmentioning

confidence: 99%

“…Good conversions (from 75 up to 100 %) have been obtained with ten ketones bearing electron withdrawing substituents (α‐hydroxy or another carbonyl group), whereas no conversion was observed under the same experimental conditions when non‐activated ketones were used. For five aldols, enantiomeric excesses, diastereoisomeric ratio and absolute configuration of the stereocenters have been determined (Table ) …”

Section: Cross‐aldol Additionsmentioning

confidence: 99%

Building Up Quaternary Stereocenters Through Biocatalyzed Direct Insertion of Carbon Nucleophiles on Ketones

Gaggero

2019

Eur J Org Chem

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Quaternary stereocenters are privileged structural motifs, widely distributed in natural products and in pharmaceutically active compounds. Asymmetric methods for the efficient construction of these prominent frameworks are rapidly increasing. Biocatalysis represents an alternative to the existing methods of using hazardous metals and chemicals. Enzymes discussed in this mini-review involve thiamine-bisphosphate (ThDP)-dependent lyases, aldolases and hydroxynitrile lyases.[a] 7616 of CO 2 is transferred to the si face of an aldehyde acceptor to give an (R)-hydroxy ketone (Scheme 2). Scheme 2. Catalytic cycle of ThDP-dependent acyloin reaction.

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Synthesis of Branched‐Chain Sugars with a DHAP‐Dependent Aldolase: Ketones are Electrophile Substrates of Rhamnulose‐1‐phosphate Aldolases

Cited by 23 publications

References 49 publications

Biosynthesis of dendroketose from different carbon sources using in vitro and in vivo metabolic engineering strategies

Biosynthesis of dendroketose from different carbon sources using in vitro and in vivo metabolic engineering strategies

Revisiting the methionine salvage pathway and its paralogues

Building Up Quaternary Stereocenters Through Biocatalyzed Direct Insertion of Carbon Nucleophiles on Ketones

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