Crystallization and preliminary X-ray diffraction analysis of AntE, a crotonyl-CoA carboxylase/reductase from<i>Streptomyces</i>sp. NRRL 2288

Zhang, Lihan; Chen, Jing; Mori, Takeo; Yan, Yan; Li, Wen; Abe, Ikuro

doi:10.1107/s2053230x14008371

Cited by 3 publications

(1 citation statement)

References 16 publications

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“…By replacing the selectivity-conferring residues (V163 and V362, numbers corresponding to CinF) with smaller residues such as glycines, these CCRs may be able to accept bulky aromatic substrates. Currently, several structures of broad-selective CCRs have been made available. , On the basis of the protein structures, directed evolution at these sites could highly effective in expand CCR’s selectivity scope. It is believed that the strategy disclosed here can be readily tailored to convert other amino acids including tyrosine, histidine and aspartic acid into CoA-linked extender units.…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Formation and Selection of Benzylmalonyl-CoA from the Biosynthesis of Splenocin and Enterocin Reveals a Versatile Way to Introduce Amino Acids into Polyketide Carbon Scaffolds

et al. 2015

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Selective modification of carbon scaffolds via biosynthetic engineering is important for polyketide structural diversification. Yet, this scope is currently restricted to simple aliphatic groups due to (1) limited variety of CoA-linked extender units, which lack aromatic structures and chemical reactivity, and (2) narrow acyltransferase (AT) specificity, which is limited to aliphatic CoA-linked extender units. In this report, we uncovered and characterized the first aromatic CoA-linked extender unit benzylmalonyl-CoA from the biosynthetic pathways of splenocin and enterocin in Streptomyces sp. CNQ431. Its synthesis employs a deamination/reductive carboxylation strategy to convert phenylalanine into benzylmalonyl-CoA, providing a link between amino acid and CoA-linked extender unit synthesis. By characterization of its selection, we further validated that AT domains of splenocin, and antimycin polyketide synthases are able to select this extender unit to introduce the phenyl group into their dilactone scaffolds. The biosynthetic machinery involved in the formation of this extender unit is highly versatile and can be potentially tailored for tyrosine, histidine and aspartic acid. The disclosed aromatic extender unit, amino acid-oriented synthetic pathway, and aromatic-selective AT domains provides a systematic breakthrough toward current knowledge of polyketide extender unit formation and selection, and also opens a route for further engineering of polyketide carbon scaffolds using amino acids.

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Section: Discussionmentioning

confidence: 99%