TY - JOUR
T1 - Lessons learned from the transformation of natural product discovery to a genome-driven endeavor
AU - Deane, Caitlin D.
AU - Mitchell, Douglas A.
N1 - Funding Information:
We thank members of the Mitchell lab for the critical review of this manuscript. C.D.D. is supported by the Robert C. and Carolyn J. Springborn Endowment. D.A.M. is supported by the US National Institutes of Health (NIH, 1R01 GM097142) and the NIH Director’s New Innovator Award Program (DP2 OD008463).
PY - 2014/2
Y1 - 2014/2
N2 - Natural product discovery is currently undergoing a transformation from a phenotype-driven field to a genotype-driven one. The increasing availability of genome sequences, coupled with improved techniques for identifying biosynthetic gene clusters, has revealed that secondary metabolomes are strikingly vaster than previously thought. New approaches to correlate biosynthetic gene clusters with the compounds they produce have facilitated the production and isolation of a rapidly growing collection of what we refer to as "reverse- discovered" natural products, in analogy to reverse genetics. In this review, we present an extensive list of reverse-discovered natural products and discuss seven important lessons for natural product discovery by genome-guided methods: structure prediction, accurate annotation, continued study of model organisms, avoiding genome-size bias, genetic manipulation, heterologous expression, and potential engineering of natural product analogs.
AB - Natural product discovery is currently undergoing a transformation from a phenotype-driven field to a genotype-driven one. The increasing availability of genome sequences, coupled with improved techniques for identifying biosynthetic gene clusters, has revealed that secondary metabolomes are strikingly vaster than previously thought. New approaches to correlate biosynthetic gene clusters with the compounds they produce have facilitated the production and isolation of a rapidly growing collection of what we refer to as "reverse- discovered" natural products, in analogy to reverse genetics. In this review, we present an extensive list of reverse-discovered natural products and discuss seven important lessons for natural product discovery by genome-guided methods: structure prediction, accurate annotation, continued study of model organisms, avoiding genome-size bias, genetic manipulation, heterologous expression, and potential engineering of natural product analogs.
KW - Biosynthetic gene clusters
KW - Genetic manipulation
KW - Genome mining
KW - Heterologous expression
KW - Natural products
KW - Reverse discovery
KW - Structure prediction
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U2 - 10.1007/s10295-013-1361-8
DO - 10.1007/s10295-013-1361-8
M3 - Review article
C2 - 24142337
AN - SCOPUS:84893490856
VL - 41
SP - 315
EP - 331
JO - Journal of Industrial Microbiology and Biotechnology
JF - Journal of Industrial Microbiology and Biotechnology
SN - 1367-5435
IS - 2
ER -