Cell-Free Exploration of the Natural Product Chemical Space

Jonathan W. Bogart, Maria D. Cabezas, Bastian Vögeli, Derek A. Wong, Ashty S. Karim, Michael C. Jewett*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

Natural products and secondary metabolites comprise an indispensable resource from living organisms that have transformed areas of medicine, agriculture, and biotechnology. Recent advances in high-throughput DNA sequencing and computational analysis suggest that the vast majority of natural products remain undiscovered. To accelerate the natural product discovery pipeline, cell-free metabolic engineering approaches used to develop robust catalytic networks are being repurposed to access new chemical scaffolds, and new enzymes capable of performing diverse chemistries. Such enzymes could serve as flexible biocatalytic tools to further expand the unique chemical space of natural products and secondary metabolites, and provide a more sustainable route to manufacture these molecules. Herein, we highlight select examples of natural product biosynthesis using cell-free systems and propose how cell-free technologies could facilitate our ability to access and modify these structures to transform synthetic and chemical biology.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalChemBioChem
Volume22
Issue number1
DOIs
StatePublished - Jan 5 2021

Funding

We acknowledge support from the National Institutes of Health grant 1U19AI142780-01, the DARPA 1000 Molecules Program HR0011-15-C-0084, the Department of Energy grant DE-SC0018249, the Office of Energy Efficiency and Renewable Energy grant DE-EE0008343, the David and Lucile Packard Foundation, and the Camille Dreyfus Teacher-Scholar Program. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of DARPA or the U.S. Government. B.V. acknowledges support from the SNSF Early Postdoc.Mobility fellowship P2SKP3_184036. D.A.W. acknowledges support from the National Science Foundation Graduate Research Fellowship under grant no. DGE-1842165. We acknowledge support from the National Institutes of Health grant 1U19AI142780‐01, the DARPA 1000 Molecules Program HR0011‐15‐C‐0084, the Department of Energy grant DE‐SC0018249, the Office of Energy Efficiency and Renewable Energy grant DE‐EE0008343, the David and Lucile Packard Foundation, and the Camille Dreyfus Teacher‐Scholar Program. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of DARPA or the U.S. Government. B.V. acknowledges support from the SNSF Early Postdoc.Mobility fellowship P2SKP3_184036. D.A.W. acknowledges support from the National Science Foundation Graduate Research Fellowship under grant no. DGE‐1842165.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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