RiPP antibiotics: biosynthesis and engineering potential.
RiPP antibiotics: biosynthesis and engineering potential.
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DOI：
10.1016/j.mib.2018.02.010
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发表时间：
2018-10
影响因子：
5.4
通讯作者：
Mitchell DA
中科院分区：
文献类型：
--
作者：
Hudson GA;Mitchell DA
抗生素耐药性细菌感染的威胁继续强调需要新的治疗方案。从历史上看，来自微生物的小分子代谢物提供了丰富的抗生素化合物来源，因此，已经投入了大量的努力来工程化负责任的生物合成途径，以产生具有吸引人的药理学性质的新型类似物。不幸的是，生物合成严格性限制了非核糖体肽合成酶和聚酮酶大量产生实质上不同的类似物的能力。另一类天然产物，核糖体合成和后修饰的肽（RIPPs），近年来迅速扩大，许多天然显示出强大的抗生素活性。RiPP生物合成途径是模块化的，本质上对替代底物具有耐受性。几个突出的RIPPs与抗生素活性将涵盖在这篇评论中，重点是他们的生物合成可塑性。虽然只有少数RiPP酶在机械上得到了彻底的研究，但这些知识已经被用来产生新的天然化合物。通过使用合成生物学方法，RiPP工程的持续努力在释放这种天然产品类别的潜力方面具有很大的希望。
The threat of antibiotic resistant bacterial infections continues to underscore the need for new treatment options. Historically, small molecule metabolites from microbes have provided a rich source of antibiotic compounds, and as a result, significant effort has been invested in engineering the responsible biosynthetic pathways to generate novel analogs with attractive pharmacological properties. Unfortunately, biosynthetic stringency has limited the capacity of non-ribosomal peptide synthetases and polyketide synthases from producing substantially different analogs in large numbers. Another class of natural products, the ribosomally synthesized and post-translationally modified peptides (RiPPs), have rapidly expanded in recent years with many natively displaying potent antibiotic activity. RiPP biosynthetic pathways are modular and intrinsically tolerant to alternative substrates. Several prominent RiPPs with antibiotic activity will be covered in this review with a focus on their biosynthetic plasticity. While only a few RiPP enzymes have been thoroughly investigated mechanistically, this knowledge has already been harnessed to generate new-to-nature compounds. Through the use of synthetic biology approaches, on-going efforts in RiPP engineering hold great promise in unlocking the potential of this natural product class.
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影响因子：
18.2
作者：
Burkhart BJ;Kakkar N;Hudson GA;van der Donk WA;Mitchell DA
通讯作者：
Mitchell DA
影响因子：
4
作者：
Deane, Caitlin D.;Melby, Joel O.;Molohon, Katie J.;Susarrey, Aziz R.;Mitchell, Douglas A.
通讯作者：
Mitchell, Douglas A.
影响因子：
--
作者：
Hayashi, Shohei;Ozaki, Taro;Onaka, Hiroyasu
通讯作者：
Onaka, Hiroyasu
DOI：
10.1073/pnas.0913677107
发表时间：
2010-06-08
影响因子：
11.1
作者：
Li, Bo;Sher, Daniel;van der Donk, Wilfred A.
通讯作者：
van der Donk, Wilfred A.
影响因子：
15
作者：
Hegemann, Julian D.;Zimmermann, Marcel;Marahiel, Mohamed A.
通讯作者：
Marahiel, Mohamed A.