National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
R37 GM058822
米国
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
F32 GM129944
米国
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
F32 GM120868
米国
引用
ジャーナル: Science / 年: 2019 タイトル: Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products. 著者: Chi P Ting / Michael A Funk / Steve L Halaby / Zhengan Zhang / Tamir Gonen / Wilfred A van der Donk / 要旨: 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.