metabolic engineering

cell factories

piecewise

heterologous

insertion loss

dna assembly

factories

polyketide

transposable elements

gene clusters

legal

front matter abstract_90768

subungual

biochem

agricultural_43883

elucidation

biosynthetic genes

Biotechnology Advances

With the rapidly growing number of sequenced microbial (meta)genomes, enormous cryptic natural product (NP) biosynthetic gene clusters (BGCs) have been identified, which are regarded as a rich reservoir for novel drug discovery. A series of powerful tools for engineering BGCs has accelerated the discovery and development of pharmaceutically active NPs. Here, we describe recent advances in the strategies for BGCs manipulation, which are driven by emerging technologies, including efficient DNA recombination systems, versatile CRISPR/Cas9 genome editing tools and diverse DNA assembly methods. We further discuss how these approaches could be used for genome mining studies and industrial strain improvement.

New strategies and approaches for engineering biosynthetic gene clusters of microbial natural products