- Discovery and Engineering of Pathways for Production of α-Branched Organic Acids
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Cell-based synthesis offers many opportunities for preparing small molecules from simple renewable carbon sources by telescoping multiple reactions into a single fermentation step. One challenge in this area is the development of enzymatic carbon-carbon bond forming cycles that enable a modular disconnection of a target structure into cellular building blocks. In this regard, synthetic pathways based on thiolase enzymes to catalyze the initial carbon-carbon bond forming step between acyl coenzyme A (CoA) substrates offer a versatile route for biological synthesis, but the substrate diversity of such pathways is currently limited. In this report, we describe the identification and biochemical characterization of a thiolase-ketoreductase pair involved in production of branched acids in the roundworm, Ascaris suum, that demonstrates selectivity for forming products with an α-methyl branch using a propionyl-CoA extender unit. Engineering synthetic pathways for production of α-methyl acids in Escherichia coli using these enzymes allows the construction of microbial strains that produce either chiral 2-methyl-3-hydroxy acids (1.1 ± 0.2 g L-1) or branched enoic acids (1.12 ± 0.06 g L-1) in the presence of a dehydratase at 44% and 87% yield of fed propionate, respectively. In vitro characterization along with in vivo analysis indicates that the ketoreductase is the key driver for selectivity, forming predominantly α-branched products even when paired with a thiolase that highly prefers unbranched linear products. Our results expand the utility of thiolase-based pathways and provide biosynthetic access to α-branched compounds as precursors for polymers and other chemicals.
- Blaisse, Michael R.,Dong, Hongjun,Fu, Beverly,Chang, Michelle C. Y.
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supporting information
p. 14526 - 14532
(2017/10/24)
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- The direct thioesterification of aldehydes with disulfides via NHC-catalyzed carbonyl umpolung strategy
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An efficient N-heterocyclic carbene (NHC)-catalyzed direct thioesterification of aldehydes and α,β-unsaturated aldehydes (enals) with diaryl disulfides is reported. The protocol involves carbonyl umpolung reactivity of aldehydes and enals in which the car
- Singh, Santosh,Yadav, Lal Dhar S.
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experimental part
p. 5136 - 5140
(2012/09/22)
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- Ionic liquid: An efficient and reusable media for seleno- and thioester synthesis promoted by indium
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A series of thio and selenoesters were efficiently obtained employing stable diorganyl chalcogenides, acyl chlorides, and In as reducing agent in BMIM·PF6. Recycling of the ionic liquid was also performed, which was reused three times.
- Tabarelli, Greice,Alberto, Eduardo E.,Deobald, Anna M.,Marin, Graciane,Rodrigues, Oscar E.D.,Dornelles, Luciano,Braga, Antonio L.
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experimental part
p. 5728 - 5731
(2010/11/16)
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- Zinc promoted convenient and general synthesis of thiol esters
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Synthesis of thiol esters from acyl chlorides and thiols in the presence of activated zinc is described. The recovery of zinc and its reuse makes the procedure more economic.
- Meshram,Reddy, Gondi Sudershan,Bindu, K. Hima,Yadav
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p. 877 - 878
(2007/10/03)
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- Diels-Alder reactions of α,β-unsaturated thioesters and α,β-unsaturated selenoesters
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α,β-Unsaturated thioesters and selenoesters serve as dienophiles in Diels-Alder reactions with a variety of 1,3-dienes. Good levels of regioselectivity are obtained with unsymmetrical dienes when Lewis acid promoters are used. Thioesters and selenoesters
- Byeon, Chang-Ho,Chen, Cheng-Yi,Ellis, David A.,Hart, David J.,Li, Jing
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p. 596 - 598
(2007/10/03)
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- Insertion of Carbon Monoxide into Allylic Carbon-Sulfur Bonds Catalyzed by Palladium and Ruthenium Complexes
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The metal complex-catalyzed insertion of carbon monoxide into the C-S bond of various allylic sulfides affords thioesters in up to 88percent yield.The reaction is catalyzed by various palladium complexes, with concomitant isomerization of the olefin into conjugation with the carbonyl group.In these cases, only the trans isomer was detected by 1H NMR spectroscopy.Ruthenium complexes also catalyzed the carbonylation but the initially formed β,γ-thioester was not isomerized.
- Crudden, Cathleen M.,Alper, Howard
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p. 5579 - 5587
(2007/10/03)
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- A SIMPLE SYNTHESIS OF THIOL ESTERS FROM COPPER-I-MERCAPTIDES AND ACYL CHLORIDES
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Thiol esters are obtained from acyl chlorides and copper-I-mercaptides in excellent yields.
- Reissig, Hans-Ulrich,Scherer, Bernadette
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p. 4259 - 4262
(2007/10/02)
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