Bioengineering natural product biosynthetic pathways for therapeutic applications

Ming-Cheng Wu, Brian Law, Barrie Wilkinson, Jason Micklefield

    Research output: Contribution to journalArticlepeer-review


    With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications. © 2012 Elsevier Ltd.
    Original languageEnglish
    Pages (from-to)931-940
    Number of pages10
    JournalCurrent Opinion in Biotechnology
    Issue number6
    Publication statusPublished - Dec 2012


    • natural products
    • cryptic cluster
    • actinomycetes
    • streptomyces
    • biosynthetic pathway
    • secondary metabolites


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