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-Structure paper
Title | Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products. |
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Journal, issue, pages | Science, Vol. 365, Issue 6450, Page 280-284, Year 2019 |
Publish date | Jul 19, 2019 |
![]() | Chi P Ting / Michael A Funk / Steve L Halaby / Zhengan Zhang / Tamir Gonen / Wilfred A van der Donk / ![]() |
PubMed Abstract | Genome sequencing of environmental bacteria allows identification of biosynthetic gene clusters encoding unusual combinations of enzymes that produce unknown natural products. We identified a pathway ...Genome sequencing of environmental bacteria allows identification of biosynthetic gene clusters encoding unusual combinations of enzymes that produce unknown natural products. We identified a pathway in which a ribosomally synthesized small peptide serves as a scaffold for nonribosomal peptide extension and chemical modification. Amino acids are transferred to the carboxyl terminus of the peptide through adenosine triphosphate and amino acyl-tRNA-dependent chemistry that is independent of the ribosome. Oxidative rearrangement, carboxymethylation, and proteolysis of a terminal cysteine yields an amino acid-derived small molecule. Microcrystal electron diffraction demonstrates that the resulting product is isosteric to glutamate. We show that a similar peptide extension is used during the biosynthesis of the ammosamides, which are cytotoxic pyrroloquinoline alkaloids. These results suggest an alternative paradigm for biosynthesis of amino acid-derived natural products. |
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Methods | EM (electron crystallography) |
Resolution | 1 Å |
Structure data | EMDB-20411, PDB-6po6: |
Chemicals | ![]() ChemComp-HOH: |
Source |
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![]() | UNKNOWN FUNCTION / Ribosomal synthesized small peptide / MicroED / microcrystal electron diffraction |