2015
DOI: 10.1038/nchem.2308
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Use of a biosynthetic intermediate to explore the chemical diversity of pseudo-natural fungal polyketides

Abstract: The structural complexity and diversity of natural products make them attractive sources for potential drug discovery, with their characteristics being derived from the multi-step combination of enzymatic and non-enzymatic conversions of intermediates in each biosynthetic pathway. Intermediates that exhibit multipotent behaviour have great potential for use as starting points in diversity-oriented synthesis. Inspired by the biosynthetic pathways that form complex metabolites from simple intermediates, we devel… Show more

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Cited by 80 publications
(52 citation statements)
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“…Presumably, the tle gene cluster derivatives were biosynthesized by a cytochrome P450 in S. lividans , by an acyltransferase in S. albus , and by a multifunctional P450 in S. avermitilis . Because natural product intermediates can serve as branch points of various biosynthetic pathways, the utilization of this multipotency might accelerate access to new compounds, as recently described by Oshima and co‐workers in the case of a fungal heterologous expression system . In light of this, systematic heterologous expression with multiple available hosts would be a convenient method for exploiting the new chemical space of natural product scaffolds.…”
Section: Methodsmentioning
confidence: 99%
“…Presumably, the tle gene cluster derivatives were biosynthesized by a cytochrome P450 in S. lividans , by an acyltransferase in S. albus , and by a multifunctional P450 in S. avermitilis . Because natural product intermediates can serve as branch points of various biosynthetic pathways, the utilization of this multipotency might accelerate access to new compounds, as recently described by Oshima and co‐workers in the case of a fungal heterologous expression system . In light of this, systematic heterologous expression with multiple available hosts would be a convenient method for exploiting the new chemical space of natural product scaffolds.…”
Section: Methodsmentioning
confidence: 99%
“…[22] Genome sequencing of Streptomyces sp.QL37 allowed the identification of atype II PKS gene cluster (lug,Supporting Information, Table S7 and Figure S7). [22] Genome sequencing of Streptomyces sp.QL37 allowed the identification of atype II PKS gene cluster (lug,Supporting Information, Table S7 and Figure S7).…”
Section: Angewandte Chemiementioning
confidence: 99%
“…10 And Asai et al expressed a partial NR-PKS gene from Chaetomium indicum in Aspergillus oryzae to obtain a reactive intermediate that was then used as a starting point for diverse synthesis, producing a variety of ‘pseudonatural’ products. 21 …”
Section: Before Mass Spectrometrymentioning
confidence: 99%
“…20, 21 This stands in contrast with the primary metabolomics community, where robust mass spectrometry workflows have been developed to routinely identify and quantify hundreds of metabolites in central metabolism. 22-24 Our goal here is not to review the fundamentals of mass spectrometry.…”
Section: Introductionmentioning
confidence: 99%