Library construction and targeted BGC screening for more efficient discovery of microbial natural products
Microbial natural products(NPs)are a major source for mining small molecule drugs,which have been widely used in medicine,agriculture,and other fields.Growing antimicrobial resistance and other public health problems necessitate the rapid discovery of microbial NPs with novel structures and bioactivities.With rapid advances in high-throughput screening and low-cost DNA sequencing technologies,highly diverse biosynthetic gene clusters(BGCs)have been detected in bacteria and fungi,but characterized compounds are limited,representing the tip of an iceberg,and much more novel small molecules are awaiting for being discovered.Although various strategies have been developed for NP discovery,effectively linking the biosynthetic pathways to their encoded products remains a challenge.Recently,(meta)genomic library construction strategies have shown advantages in elucidating NP biosynthetic pathways more efficiently,and significantly accelerated the discovery of novel NPs by combining with high-efficient targeted BGC screening approaches.In this review,we summarize three strategies for discovering microbial NPs based on(meta)genomic library construction and targeted BGC screening.We also discuss the cloning vectors including Cosmid/Fosmid,BAC/PAC and FAC/YAC,and comment strategies for library construction and targeted BGC screening,such as LEXAS and CONKAT-Seq.Furthermore,we compare strengths,limitations,and applicability of different libraries.At the end,we prospect the future developments of these strategies for the high-throughput discovery of microbial NPs.
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