title: Strain prioritization for natural product discovery by a high-throughput real-time PCR method.
abstract: Natural products offer unmatched chemical and structural diversity compared to other small-molecule libraries, but traditional natural product discovery programs are not sustainable, demanding too much time, effort, and resources. Here we report a strain prioritization method for natural product discovery. Central to the method is the application of real-time PCR, targeting genes characteristic to the biosynthetic machinery of natural products with distinct scaffolds in a high-throughput format. The practicality and effectiveness of the method were showcased by prioritizing 1911 actinomycete strains for diterpenoid discovery. A total of 488 potential diterpenoid producers were identified, among which six were confirmed as platensimycin and platencin dual producers and one as a viguiepinol and oxaloterpin producer. While the method as described is most appropriate to prioritize strains for discovering specific natural products, variations of this method should be applicable to the discovery of other classes of natural products. Applications of genome sequencing and genome mining to the high-priority strains could essentially eliminate the chance elements from traditional discovery programs and fundamentally change how natural products are discovered.
authors.affiliation: Department of Chemistry, ∇Department of Molecular Therapeutics, and #Natural Products Library Initiative, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.lastname: Hindra
authors.forename: Tingting
authors.initials: T
authors.lastname: Huang
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rudolf
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xie
authors.forename: Guangbo
authors.initials: G
authors.lastname: Xie
authors.forename: Qihui
authors.initials: Q
authors.lastname: Teng
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Lohman
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Li-Xing
authors.initials: LX
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Duan
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D039903:Actinobacteria / Q000737:chemistry*; D000218:Adamantane / Q000737:chemistry; D062365:Aminobenzoates / Q000737:chemistry; D000627:Aminophenols / Q000737:chemistry; D000813:Anilides / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry*; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D054852:Small Molecule Libraries
chemical_list: D062365:Aminobenzoates; D000627:Aminophenols; D000813:Anilides; D001688:Biological Products; D011083:Polycyclic Compounds; D054852:Small Molecule Libraries; D000218:Adamantane; C510909:platensimycin; C520340:platencin