Understanding thioamitide biosynthesis using pathway engineering and untargeted metabolomics.
Understanding thioamitide biosynthesis using pathway engineering and untargeted metabolomics.
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DOI：
10.1039/d0sc06835g
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发表时间：
2021-04-19
期刊：
影响因子：
8.4
通讯作者：
Truman AW
中科院分区：
文献类型：
--
作者：
Eyles TH;Vior NM;Lacret R;Truman AW
Thiostreptamide S4 is a thioamitide, a family of promising antitumour ribosomally synthesised and post-translationally modified peptides (RiPPs). The thioamitides are one of the most structurally complex RiPP families, yet very few thioamitide biosynthetic steps have been elucidated, even though the biosynthetic gene clusters (BGCs) of multiple thioamitides have been identified. We hypothesised that engineering the thiostreptamide S4 BGC in a heterologous host could provide insights into its biosynthesis when coupled with untargeted metabolomics and targeted mutations of the precursor peptide. Modified BGCs were constructed, and in-depth metabolomics enabled a detailed understanding of the biosynthetic pathway to thiostreptamide S4, including the identification of a protein critical for amino acid dehydration that has homology to HopA1, an effector protein used by a plant pathogen to aid infection. We use this biosynthetic understanding to bioinformatically identify diverse RiPP-like BGCs, paving the way for future RiPP discovery and engineering. Heterologous expression, pathway mutations and detailed metabolomic analysis were used to deduce a model for the biosynthesis of thiostreptamide S4, which belongs the thioamitide family of antitumour RiPPs.
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影响因子：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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DOI：
10.1107/s0907444903011831
发表时间：
2003-08-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
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作者：
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通讯作者：
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