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