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Engineering Biosynthesis of Non-ribosomal Peptides and Polyketides by Directed Evolution

[ Vol. 16 , Issue. 15 ]


Zhe Rui and Wenjun Zhang   Pages 1755 - 1762 ( 8 )


Non-ribosomal peptides (NRPs) and polyketides (PKs) play key roles in pharmaceutical industry due to their promising biological activities. The structural complexity of NRPs and PKs, however, creates significant synthetic challenges for producing these natural products and their analogues by purely chemical means. Alternatively, difficult syntheses can be achieved by using biosynthetic enzymes with improved efficiency and altered selectivity that are acquired from directed evolution. Key to the successful directed evolution is the methodology of screening/selection. This review summarizes the screening/selection strategies that have been employed to improve or modify the functions of non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), in the hope of triggering the wide adoption of the directed evolution approaches in the engineered biosynthesis of NRPs and PKs for drug discovery.


Biosynthesis, Directed evolution, High-throughput screening, Mutasynthesis, Natural product, Non-ribosomal peptide synthetase, Polyketide synthase.


Department of chemical and biomolecular engineering, University of California, Berkeley, CA 94720; Physical biosciences division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720

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