Leveraging a large microbial strain collection for natural product discovery

Throughout history, natural products have significantly contributed to the discovery of novel chemistry, drug leads, and tool molecules to probe and address complex challenges in biology and medicine. Recent microbial genome sequencing efforts have uncovered many microbial biosynthetic gene clusters...

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Bibliographic Details
Published in:The Journal of biological chemistry 2019-11, Vol.294 (45), p.16567-16576
Main Authors: Steele, Andrew D., Teijaro, Christiana N., Yang, Dong, Shen, Ben
Format: Article
Language:English
Subjects:
Adamantane - chemistry
Adamantane - metabolism
Aminobenzoates - chemistry
Aminobenzoates - metabolism
Anilides - chemistry
Anilides - metabolism
Bacteria - genetics
Bacteria - metabolism
bioinformatics
Biological Products - chemistry
Biological Products - metabolism
biosynthesis
Computational Biology - methods
Databases, Genetic
drug screening
function-centric approaches
Fungi - genetics
Fungi - metabolism
genome mining
Genome, Bacterial
high-throughput screening (HTS)
JBC Reviews
microbial strain collection
Multigene Family
natural product
strain prioritization
structure-centric
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Summary:Throughout history, natural products have significantly contributed to the discovery of novel chemistry, drug leads, and tool molecules to probe and address complex challenges in biology and medicine. Recent microbial genome sequencing efforts have uncovered many microbial biosynthetic gene clusters without an associated natural product. This means that the natural products isolated to date do not fully reflect the biosynthetic potential of microbial strains. This observation has rejuvenated the natural product community and inspired a return to microbial strain collections. Mining large microbial strain collections with the most current technologies in genome sequencing, bioinformatics, and high-throughput screening techniques presents new opportunities in natural product discovery. In this review, we report on the newly expanded microbial strain collection at The Scripps Research Institute, which represents one of the largest and most diverse strain collections in the world. Two complementary approaches, i.e. structure-centric and function-centric, are presented here to showcase how to leverage a large microbial strain collection for natural product discovery and to address challenges and harness opportunities for future efforts. Highlighted examples include the discovery of alternative producers of known natural products with superior growth characteristics and high titers, novel analogs of privileged scaffolds, novel natural products, and new activities of known and new natural products. We anticipate that this large microbial strain collection will facilitate the discovery of new natural products for many applications.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.REV119.006514