Characterization of 2-Octenoyl-CoA Carboxylase/Reductase Utilizing<i>pteB</i>from<i>Streptomyce avermitilis</i>

Yoo, Hye-Gyeong; Kwon, Soyeon; Kim, Suji; Karki, Suman; Park, Chul–Seung; Kwon, Hyung‐Jin

doi:10.1271/bbb.110003

Cited by 21 publications

(10 citation statements)

References 11 publications

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“…A homolog of the latter enzyme was also shown to be responsible for the synthesis of the unusual extender units chloroethylmalonyl-CoA (from chlorocrotonyl-CoA) and propylmalonyl-CoA (from 2-pentenylCoA) (46,80). Moreover, in the biosynthesis of the proteasome inhibitor cinnabaramide A and the macrolide antibiotic filipin, CCR homologs supply hexylmalonyl-CoA via reductive carboxylation of 2-octenoyl-CoA (97,112,130).…”

Section: Carboxylases In Biosynthetic Pathwaysmentioning

confidence: 99%

“…Similarly, CCR was shown to provide ethylmalonyl-CoA for an engineered carboxymethylproline synthase in vitro, yielding new precursors for carbapenem antibiotic synthesis (58). In addition, some CCR homologs show relaxed substrate specificities (42,80,130), which makes these enzymes attractive for future use in combinatorial biosynthesis.…”

Section: Carboxylases In Synthetic Microbial Pathwaysmentioning

confidence: 99%

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Carboxylases in Natural and Synthetic Microbial Pathways

Erb

2011

Appl Environ Microbiol

183

165

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Carboxylases are among the most important enzymes in the biosphere, because they catalyze a key reaction in the global carbon cycle: the fixation of inorganic carbon (CO 2 ). This minireview discusses the physiological roles of carboxylases in different microbial pathways that range from autotrophy, carbon assimilation, and anaplerosis to biosynthetic and redox-balancing functions. In addition, the current and possible future uses of carboxylation reactions in synthetic biology are discussed. Such uses include the possible transformation of the greenhouse gas carbon dioxide into value-added compounds and the production of novel antibiotics.

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Section: Carboxylases In Biosynthetic Pathwaysmentioning

confidence: 99%

Section: Carboxylases In Synthetic Microbial Pathwaysmentioning

confidence: 99%

Carboxylases in Natural and Synthetic Microbial Pathways

Erb

2011

Appl Environ Microbiol

183

165

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“…5), filipin III ( n -hexylmalonyl-CoA) (ref. 6), antimycins ( n -butylmalonyl-CoA, n -hexylmalony-CoA) (ref. 7), splenocins (benzylmalonyl-CoA) (ref.…”

mentioning

confidence: 99%

“…In all of these examples, the final step of unusual extender unit biosynthesis is catalysed by a homologue of crotonyl-CoA reductase/carboxylase (CCRC) and involves NADPH-mediated reduction of an α, β-unsaturated thioester, followed by trapping of the resulting enolate by reaction with carbon dioxide121314. The genes encoding such CCRC homologues are invariably clustered with the genes encoding the polyketide synthases they supply4567891011. Remarkably, no genes encoding CCRC homologues can be found in the stambomycin biosynthetic gene cluster (BGC) (ref.…”

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confidence: 99%

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

et al. 2016

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Type I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of a, b-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemicallysynthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual b-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues.

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“…35–37 Selected for by AT domains within the PKS (either by cis -acting or trans -acting ATs), these malonate derivatives can be linked to either CoA or a standalone ACP via a thioester linkage. 9 The biosynthesis of atypical PKS extender units is generally encoded within the biosynthetic gene cluster of the secondary metabolite into which they are incorporated.…”

Section: Polyketide Extender Unitsmentioning

confidence: 99%

Recent advances in the biosynthesis of unusual polyketide synthase substrates

Ray

Moore

2016

Nat. Prod. Rep.

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Covering: 2003 to July 2015 for polyketide synthase starter units and 2012 to September 2015 for polyketide synthase extender units This highlight provides an overview of recent advances in understanding the diversity of polyketide synthase (PKS) substrate building blocks. Substrates functioning as starter units and extender units contribute significantly to the chemical complexity and structural diversity exhibited by this class of natural products. This article complements and extends upon the current comprehensive reviews that have been published on these two topics (Moore and Hertweck, Nat. Prod. Rep., 2002, 19, 70; Chan et. al., Nat. Prod. Rep., 2009, 1, 90; Wilson and Moore, Nat. Prod. Rep., 2012, 29, 72).

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Characterization of 2-Octenoyl-CoA Carboxylase/Reductase UtilizingpteBfromStreptomyce avermitilis

Cited by 21 publications

References 11 publications

Carboxylases in Natural and Synthetic Microbial Pathways

Carboxylases in Natural and Synthetic Microbial Pathways

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

Recent advances in the biosynthesis of unusual polyketide synthase substrates

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