Biosynthetic potential-based strain prioritization for natural product discovery: a showcase for diterpenoid-producing actinomycetes

Pengfei Xie, Ming Ma, Mostafa E Rateb, Khaled A Shaaban, Zhiguo Yu, Sheng-Xiong Huang, Li-Xing Zhao, Xiangcheng Zhu, Yijun Yan, Ryan M Peterson, Jeremy R Lohman, Dong Yang, Min Yin, Jeffrey D Rudolf, Yi Jiang, Yanwen Duan, Ben Shen, Mostafa Ezzat Mohamed Rateb

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for the natural product community is to discover novel natural products efficiently and cost effectively. Here we report the development of a practical method to survey biosynthetic potential in microorganisms, thereby identifying the most promising strains and prioritizing them for natural product discovery. Central to our approach is the innovative preparation, by a two-tiered PCR method, of a pool of pathway-specific probes, thereby allowing the survey of all variants of the biosynthetic machineries for the targeted class of natural products. The utility of the method was demonstrated by surveying 100 strains, randomly selected from our actinomycete collection, for their biosynthetic potential of four classes of natural products, aromatic polyketides, reduced polyketides, nonribosomal peptides, and diterpenoids, identifying 16 talented strains. One of the talented strains, Streptomyces griseus CB00830, was finally chosen to showcase the discovery of the targeted classes of natural products, resulting in the isolation of three diterpenoids, six nonribosomal peptides and related metabolites, and three polyketides. Variations of this method should be applicable to the discovery of other classes of natural products.

Original languageEnglish
Pages (from-to)377-387
Number of pages11
JournalJournal of Natural Products
Volume77
Issue number2
Early online date31 Jan 2014
DOIs
Publication statusPublished - 28 Feb 2014

Fingerprint

Actinobacteria
Diterpenes
Biological Products
Polyketides
Streptomyces griseus
Biological Phenomena
Peptides
Surveying
Metabolites
Pharmaceutical Preparations
Microorganisms
Costs and Cost Analysis
Polymerase Chain Reaction
Molecules

Keywords

  • Actinobacteria
  • Biological Products
  • Diterpenes
  • Drug Discovery
  • Molecular Structure
  • Polyketide Synthases
  • Polyketides
  • Polymerase Chain Reaction
  • Streptomyces griseus

Cite this

Biosynthetic potential-based strain prioritization for natural product discovery : a showcase for diterpenoid-producing actinomycetes. / Xie, Pengfei; Ma, Ming; Rateb, Mostafa E; Shaaban, Khaled A; Yu, Zhiguo; Huang, Sheng-Xiong; Zhao, Li-Xing; Zhu, Xiangcheng; Yan, Yijun; Peterson, Ryan M; Lohman, Jeremy R; Yang, Dong; Yin, Min; Rudolf, Jeffrey D; Jiang, Yi; Duan, Yanwen; Shen, Ben; Rateb, Mostafa Ezzat Mohamed.

In: Journal of Natural Products, Vol. 77, No. 2, 28.02.2014, p. 377-387.

Research output: Contribution to journalArticle

Xie, P, Ma, M, Rateb, ME, Shaaban, KA, Yu, Z, Huang, S-X, Zhao, L-X, Zhu, X, Yan, Y, Peterson, RM, Lohman, JR, Yang, D, Yin, M, Rudolf, JD, Jiang, Y, Duan, Y, Shen, B & Rateb, MEM 2014, 'Biosynthetic potential-based strain prioritization for natural product discovery: a showcase for diterpenoid-producing actinomycetes', Journal of Natural Products, vol. 77, no. 2, pp. 377-387. https://doi.org/10.1021/np401063s
Xie, Pengfei ; Ma, Ming ; Rateb, Mostafa E ; Shaaban, Khaled A ; Yu, Zhiguo ; Huang, Sheng-Xiong ; Zhao, Li-Xing ; Zhu, Xiangcheng ; Yan, Yijun ; Peterson, Ryan M ; Lohman, Jeremy R ; Yang, Dong ; Yin, Min ; Rudolf, Jeffrey D ; Jiang, Yi ; Duan, Yanwen ; Shen, Ben ; Rateb, Mostafa Ezzat Mohamed. / Biosynthetic potential-based strain prioritization for natural product discovery : a showcase for diterpenoid-producing actinomycetes. In: Journal of Natural Products. 2014 ; Vol. 77, No. 2. pp. 377-387.
@article{427079615217497f8670b0945d44633c,
title = "Biosynthetic potential-based strain prioritization for natural product discovery: a showcase for diterpenoid-producing actinomycetes",
abstract = "Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for the natural product community is to discover novel natural products efficiently and cost effectively. Here we report the development of a practical method to survey biosynthetic potential in microorganisms, thereby identifying the most promising strains and prioritizing them for natural product discovery. Central to our approach is the innovative preparation, by a two-tiered PCR method, of a pool of pathway-specific probes, thereby allowing the survey of all variants of the biosynthetic machineries for the targeted class of natural products. The utility of the method was demonstrated by surveying 100 strains, randomly selected from our actinomycete collection, for their biosynthetic potential of four classes of natural products, aromatic polyketides, reduced polyketides, nonribosomal peptides, and diterpenoids, identifying 16 talented strains. One of the talented strains, Streptomyces griseus CB00830, was finally chosen to showcase the discovery of the targeted classes of natural products, resulting in the isolation of three diterpenoids, six nonribosomal peptides and related metabolites, and three polyketides. Variations of this method should be applicable to the discovery of other classes of natural products.",
keywords = "Actinobacteria, Biological Products, Diterpenes, Drug Discovery, Molecular Structure, Polyketide Synthases, Polyketides, Polymerase Chain Reaction, Streptomyces griseus",
author = "Pengfei Xie and Ming Ma and Rateb, {Mostafa E} and Shaaban, {Khaled A} and Zhiguo Yu and Sheng-Xiong Huang and Li-Xing Zhao and Xiangcheng Zhu and Yijun Yan and Peterson, {Ryan M} and Lohman, {Jeremy R} and Dong Yang and Min Yin and Rudolf, {Jeffrey D} and Yi Jiang and Yanwen Duan and Ben Shen and Rateb, {Mostafa Ezzat Mohamed}",
note = "ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. ACKNOWLEDGMENTS This work is supported in part by the Natural Products Library Initiative at The Scripps Research Institute, NIH grant GM086184 (to B.S.), the Chinese Ministry of Education 111 Project B08034 (to Y.D.), and National High Technology Joint Research Program of China grant 2011ZX09401-001 (to Y.D.)",
year = "2014",
month = "2",
day = "28",
doi = "10.1021/np401063s",
language = "English",
volume = "77",
pages = "377--387",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Biosynthetic potential-based strain prioritization for natural product discovery

T2 - a showcase for diterpenoid-producing actinomycetes

AU - Xie, Pengfei

AU - Ma, Ming

AU - Rateb, Mostafa E

AU - Shaaban, Khaled A

AU - Yu, Zhiguo

AU - Huang, Sheng-Xiong

AU - Zhao, Li-Xing

AU - Zhu, Xiangcheng

AU - Yan, Yijun

AU - Peterson, Ryan M

AU - Lohman, Jeremy R

AU - Yang, Dong

AU - Yin, Min

AU - Rudolf, Jeffrey D

AU - Jiang, Yi

AU - Duan, Yanwen

AU - Shen, Ben

AU - Rateb, Mostafa Ezzat Mohamed

N1 - ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. ACKNOWLEDGMENTS This work is supported in part by the Natural Products Library Initiative at The Scripps Research Institute, NIH grant GM086184 (to B.S.), the Chinese Ministry of Education 111 Project B08034 (to Y.D.), and National High Technology Joint Research Program of China grant 2011ZX09401-001 (to Y.D.)

PY - 2014/2/28

Y1 - 2014/2/28

N2 - Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for the natural product community is to discover novel natural products efficiently and cost effectively. Here we report the development of a practical method to survey biosynthetic potential in microorganisms, thereby identifying the most promising strains and prioritizing them for natural product discovery. Central to our approach is the innovative preparation, by a two-tiered PCR method, of a pool of pathway-specific probes, thereby allowing the survey of all variants of the biosynthetic machineries for the targeted class of natural products. The utility of the method was demonstrated by surveying 100 strains, randomly selected from our actinomycete collection, for their biosynthetic potential of four classes of natural products, aromatic polyketides, reduced polyketides, nonribosomal peptides, and diterpenoids, identifying 16 talented strains. One of the talented strains, Streptomyces griseus CB00830, was finally chosen to showcase the discovery of the targeted classes of natural products, resulting in the isolation of three diterpenoids, six nonribosomal peptides and related metabolites, and three polyketides. Variations of this method should be applicable to the discovery of other classes of natural products.

AB - Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for the natural product community is to discover novel natural products efficiently and cost effectively. Here we report the development of a practical method to survey biosynthetic potential in microorganisms, thereby identifying the most promising strains and prioritizing them for natural product discovery. Central to our approach is the innovative preparation, by a two-tiered PCR method, of a pool of pathway-specific probes, thereby allowing the survey of all variants of the biosynthetic machineries for the targeted class of natural products. The utility of the method was demonstrated by surveying 100 strains, randomly selected from our actinomycete collection, for their biosynthetic potential of four classes of natural products, aromatic polyketides, reduced polyketides, nonribosomal peptides, and diterpenoids, identifying 16 talented strains. One of the talented strains, Streptomyces griseus CB00830, was finally chosen to showcase the discovery of the targeted classes of natural products, resulting in the isolation of three diterpenoids, six nonribosomal peptides and related metabolites, and three polyketides. Variations of this method should be applicable to the discovery of other classes of natural products.

KW - Actinobacteria

KW - Biological Products

KW - Diterpenes

KW - Drug Discovery

KW - Molecular Structure

KW - Polyketide Synthases

KW - Polyketides

KW - Polymerase Chain Reaction

KW - Streptomyces griseus

U2 - 10.1021/np401063s

DO - 10.1021/np401063s

M3 - Article

C2 - 24484381

VL - 77

SP - 377

EP - 387

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 2

ER -