TY - JOUR
T1 - Engineering of new-to-nature ribosomally synthesized and post-translationally modified peptide natural products
AU - Wu, Chunyu
AU - van der Donk, Wilfred A.
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/6
Y1 - 2021/6
N2 - Natural products have historically been important lead sources for drug development, particularly to combat infectious diseases. Increasingly, their structurally complex scaffolds are also envisioned as leads for applications for which they did not evolve, an approach aided by engineering of new-to-nature analogs. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are promising candidates for bioengineering because they are genetically encoded and their biosynthetic enzymes display significant substrate tolerance. This review highlights recent advances in the discovery of highly unusual new reactions by genome mining and the application of engineering approaches to generate and screen novel RiPP variants. Furthermore, through the use of synthetic biology approaches, hybrid molecules with enhanced or completely new activities have been identified, which opens the door for future advancement of RiPPs as potential next-generation therapeutics.
AB - Natural products have historically been important lead sources for drug development, particularly to combat infectious diseases. Increasingly, their structurally complex scaffolds are also envisioned as leads for applications for which they did not evolve, an approach aided by engineering of new-to-nature analogs. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are promising candidates for bioengineering because they are genetically encoded and their biosynthetic enzymes display significant substrate tolerance. This review highlights recent advances in the discovery of highly unusual new reactions by genome mining and the application of engineering approaches to generate and screen novel RiPP variants. Furthermore, through the use of synthetic biology approaches, hybrid molecules with enhanced or completely new activities have been identified, which opens the door for future advancement of RiPPs as potential next-generation therapeutics.
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U2 - 10.1016/j.copbio.2020.12.022
DO - 10.1016/j.copbio.2020.12.022
M3 - Review article
C2 - 33556835
AN - SCOPUS:85100399606
SN - 0958-1669
VL - 69
SP - 221
EP - 231
JO - Current Opinion in Biotechnology
JF - Current Opinion in Biotechnology
ER -