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/ange.201712851

Cited by 13 publications

(12 citation statements)

References 49 publications

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“…1, 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, 2017), using a class II aldolase-like protein that belongs to a family of promiscuous DHAP-dependent enzymes widely spread in bacteria (Laurent et al, 2018). A similar pathway may exist in other bacteria as well, but this has not been explored yet.…”

Section: A Pathway For Anaerobic Ethylene Synthesis In Bacteriamentioning

confidence: 99%

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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Section: A Pathway For Anaerobic Ethylene Synthesis In Bacteriamentioning

confidence: 99%

Revisiting the methionine salvage pathway and its paralogues

Sekowska

Ashida

Danchin

2018

Microbial Biotechnology

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“…Rhamnose-1-phosphate aldolase (RhuAs) is a dihydroxyacetone phosphate-dependent aldolase that can catalyze the cross-aldehyde condensation between dihydroxyacetone phosphate and dihydroxyacetone. Laurent et al (2018) explored the scope of electrophilic substrates for this type of enzyme, and confirmed that it has strong substrate promiscuity ( Supplementary Table 1 , entries 58–67).…”

Section: Aldolasesmentioning

confidence: 79%

Progress in Stereoselective Construction of C–C Bonds Enabled by Aldolases and Hydroxynitrile Lyases

Liu

Wei

Wen

et al. 2021

Front. Bioeng. Biotechnol.

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The creation of C–C bonds is an effective strategy for constructing complex compounds from simple synthetic blocks. Although many methods have been developed for C–C bond construction, the stereoselective creation of new C–C bonds remains a challenge. The selectivities (enantioselectivity, regioselectivity, and chemoselectivity) of biocatalysts are higher than those of chemical catalysts, therefore biocatalysts are excellent candidates for use in stereoselective C–C bond formation. Here, we summarize progress made in the past 10 years in stereoselective C–C bond formation enabled by two classic types of enzyme, aldolases and hydroxynitrile lyases. The information in this review will enable the development of new routes to the stereoselective construction of C–C bonds.

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“…Aldolase catalysed asymmetric C−C bond formation plays a pivotal role in the synthesis of many chiral building blocks, natural compounds, pharmaceuticals and has been industrially applied on a multi ton scale . Due to this wide‐ranging utility, its relevance for synthetic chemistry is well recognized .…”

Section: Introductionmentioning

confidence: 99%

CH‐π Interactions Promote the Conversion of Hydroxypyruvate in a Class II Pyruvate Aldolase

et al. 2019

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The class II hydroxy ketoacid aldolase A5VH82 from Sphingomonas wittichii RW1 (SwHKA) accepts hydroxypyruvate as nucleophilic donor substrate, giving access to synthetically challenging 3,4dihydroxy-α-ketoacids. The crystal structure of holo-SwHKA in complex with hydroxypyruvate revealed CH-π interactions between the CÀ H bonds at C3 of hydroxypyruvate and a phenylalanine residue at position 210, which in this case occupies the position of a conserved leucine residue. Mutagenesis to tyrosine further increased the electron density of the interacting aromatic system and effected a rate enhancement by twofold. While the leucine variant efficiently catalyses the enolisation of hydroxypyruvate as the first step in the aldol reaction, the enol intermediate then becomes trapped in a disfavoured configuration that considerably hinders subsequent CÀ C bond formation. In SwHKA, micromolar concentrations of inorganic phosphate increase the catalytic rate constant of enolisation by two orders of magnitude. This rate enhancement was now shown to be functionally conserved across the structurally distinct (α/β) 8 barrel and αββα sandwich folds of two pyruvate aldolases. Characterisation of the manganese (II) cofactor by electron paramagnetic resonance excluded ionic interactions between the metal centre and phosphate. Instead, histidine 44 was shown to be primarily responsible for the binding of phosphate in the micromolar range and the observed rate enhancement in SwHKA.

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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 13 publications

References 49 publications

Revisiting the methionine salvage pathway and its paralogues

Revisiting the methionine salvage pathway and its paralogues

Progress in Stereoselective Construction of C–C Bonds Enabled by Aldolases and Hydroxynitrile Lyases

CH‐π Interactions Promote the Conversion of Hydroxypyruvate in a Class II Pyruvate Aldolase

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