Research
Natural Product Genomics
Genomics-driven identification, deciphering and redesigning of natural product biosynthetic blueprints
More
than 50% of all drugs approved by the Food and Drug Administration
over the last 30 years were either natural products, natural
product-derived, or inspired by natural products. The pace of the
discovery of truly novel bioactive metabolites, however, has slowed
down significantly. Reasons for this decline are the focus on only
few talented producer phyla and the rediscovery of known molecules
using traditional bioactivity-guided screening workflows. To
circumvent the time-consuming rediscovery of known metabolites and
identify truly novel natural products in the post-genomics era, a new
discipline termed genome
mining
has been introduced. Genome mining is an in-silico
natural product discovery strategy in which sequenced genomes are
analyzed for their potential to biosynthesize natural products.
Highly sophisticated bioinformatic platforms have been developed to
identify and annotate biosynthetic gene clusters (BGCs) in genome
sequences. Despite these innovations, some natural product
biosynthetic pathways remain unrecognized by state-of-the-art
bioinformatic platforms. Moreover, for several natural product
classes, no biosynthetic rules have been implemented that allow
precise structural predictions based on genome sequence information.
The Helfrich lab employs a highly interdisciplinary approach, combining aspects of the fields of bio- and chemoinformatics, synthetic biology, microbiology, molecular biology, synthetic chemistry, and analytical chemistry, to study poorly explored natural product classes with the goal of deciphering their biosynthetic principles. Establishing biosynthetic rules governing the biosynthesis of understudied pathways will not only open up the possibility for the rational prediction of natural product structures—thereby opening up new avenues for the targeted discovery of natural products—but also pave the way towards the rational design of novel, non-natural pathways for the biosynthesis of complex natural products.
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