Genome sequences of actinomycetes have clearly demonstrated a large number of biosynthetic gene clusters potentially coding for natural products.However,most gene clusters remain cryptic.This fact prompts the concept of genome mining by developing diverse strategies to awaken those"silent"gene clusters to produce substantial amounts of natural products for structure elucidation and bioactivity evaluation,such as the change of cultivation parameters,ribosome engineering,replacement of promoters,overexpression of pathway-specific activators,and synthetic biology-guided pathway reconstitution.The success of these approaches has accelerated microbial natural product discovery and made a renaissance for interests of pharmaceutical industries in actinomycetes.
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