Reinvigorating natural product combinatorial biosynthesis with synthetic biology

被引：0
作者：
Kim E. [1 ]
Moore B.S. [2 ,3 ]
Yoon Y.J. [1 ]
机构：
[1] Department of Chemistry and Nano Science, Ewha Womans University, Seoul
[2] Scripps Institution of Oceanography, University of California at San Diego, San Diego, CA
[3] Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, CA
来源：
Nature Chemical Biology | 2015年 / 11卷 / 9期
基金：
美国国家卫生研究院; 新加坡国家研究基金会;
关键词：
D O I：
10.1038/nchembio.1893
中图分类号：
学科分类号：
摘要：
Natural products continue to play a pivotal role in drug-discovery efforts and in the understanding if human health. The ability to extend nature's chemistry through combinatorial biosynthesis - altering functional groups, regiochemistry and scaffold backbones through the manipulation of biosynthetic enzymes - offers unique opportunities to create natural product analogs. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, the realities and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development of heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry.
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收藏
页码：649 / 659
页数：10
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共 98 条
  • [11] Baltz R.H., Combinatorial biosynthesis of cyclic lipopeptide antibiotics: A model for synthetic biology to accelerate the evolution of secondary metabolite biosynthetic pathways, ACS Synth. Biol., 3, pp. 748-758, (2014)
  • [12] Sugimoto Y., Ding L., Ishida K., Hertweck C., Rational design of modular polyketide synthases: Morphing the aureothin pathway into a luteoreticulin assembly line, Angew. Chem. Int. Edn Engl., 53, pp. 1560-1564, (2014)
  • [13] Wang P., Kim W., Pickens L.B., Gao X., Tang Y., Heterologous expression and manipulation of three tetracycline biosynthetic pathways, Angew. Chem. Int. Edn Engl., 51, pp. 11136-11140, (2012)
  • [14] Wilson M.C., Moore B.S., Beyond ethylmalonyl-CoA: The functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity, Nat. Prod. Rep., 29, pp. 72-86, (2012)
  • [15] Giessen T.W., Marahiel M.A., Ribosome-independent biosynthesis of biologically active peptides: Application of synthetic biology to generate structural diversity, FEBS Lett., 586, pp. 2065-2075, (2012)
  • [16] Olano C., Mendez C., Salas J.A., Post-PKS tailoring steps in natural productproducing actinomycetes from the perspective of combinatorial biosynthesis, Nat. Prod. Rep., 27, pp. 571-616, (2010)
  • [17] Eustaquio A.S., Et al., Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-L-methionine, Proc. Natl. Acad. Sci. USA, 106, pp. 12295-12300, (2009)
  • [18] Mo S., Et al., Biosynthesis of the allylmalonyl-CoA extender unit for the FK506 polyketide synthase proceeds through a dedicated polyketide synthase and facilitates the mutasynthesis of analogues, J. Am. Chem. Soc., 133, pp. 976-985, (2011)
  • [19] Zhu X., Liu J., Zhang W., De novo biosynthesis of terminal alkyne-labeled natural products, Nat. Chem. Biol., 11, pp. 115-120, (2015)
  • [20] Yan Y., Et al., Multiplexing of combinatorial chemistry in antimycin biosynthesis: Expansion of molecular diversity and utility, Angew. Chem. Int. Edn Engl., 52, pp. 12308-12312, (2013)
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