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DOI | 10.1126/science.aau6232 |
Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products | |
Ting, Chi P.1; Funk, Michael A.2,7; Halaby, Steve L.3,4,5; Zhang, Zhengan2; Gonen, Tamir3,4,5; van der Donk, Wilfred A.1,2,6 | |
2019-07-19 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 365期号:6450页码:280-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000476479200053 |
WOS关键词 | CARRIER-PROTEIN ; INSIGHTS ; INTERMEDIATE ; COMPLEX ; TOOL |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201897 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA; 2.Univ Illinois, Dept Chem, Urbana, IL 61801 USA; 3.Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA; 4.Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA; 5.Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA; 6.Univ Illinois, Howard Hughes Med Inst, Urbana, IL 61801 USA; 7.Amer Assoc Advancement Sci, Washington, DC 20005 USA |
推荐引用方式 GB/T 7714 | Ting, Chi P.,Funk, Michael A.,Halaby, Steve L.,et al. Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products[J]. SCIENCE,2019,365(6450):280-+. |
APA | Ting, Chi P.,Funk, Michael A.,Halaby, Steve L.,Zhang, Zhengan,Gonen, Tamir,&van der Donk, Wilfred A..(2019).Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products.SCIENCE,365(6450),280-+. |
MLA | Ting, Chi P.,et al."Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products".SCIENCE 365.6450(2019):280-+. |
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