Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

A genomics-guided approach for discovering and expressing cryptic metabolic pathways

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Zazopoulos, E.
  • Huang, K. X.
  • Staffa, A.
  • Liu, W.
  • Bachmann, B. O.
  • Nonaka, K.
  • Ahlert, J.
  • Thorson, J. S.
  • Shen, Ben
  • Farnet, C. M.

publication date

  • February 2003

journal

  • Nature Biotechnology  Journal

abstract

  • Genome analysis of actinomycetes has revealed the presence of numerous cryptic gene clusters encoding putative natural products. These loci remain dormant until appropriate chemical or physical signals induce their expression. Here we demonstrate the use of a high-throughput genome scanning method to detect and analyze gene clusters involved in natural-product biosynthesis. This method was applied to uncover biosynthetic pathways encoding enediyne antitumor antibiotics in a variety of actinomycetes. Comparative analysis of five biosynthetic loci representative of the major structural classes of enediynes reveals the presence of a conserved cassette of five genes that includes a novel family of polyketide synthase (PKS). The enediyne PKS (PKSE) is proposed to be involved in the formation of the highly reactive chromophore ring structure (or "warhead") found in all enediynes. Genome scanning analysis indicates that the enediyne warhead cassette is widely dispersed among actinomycetes. We show that selective growth conditions can induce the expression of these loci, suggesting that the range of enediyne natural products may be much greater than previously thought. This technology can be used to increase the scope and diversity of natural-product discovery.

subject areas

  • Actinobacteria
  • Alkenes
  • Alkynes
  • Cells, Cultured
  • Energy Metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Genome, Bacterial
  • Micromonospora
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Streptomyces
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 1087-0156

Digital Object Identifier (DOI)

  • 10.1038/nbt784

PubMed ID

  • 12536216
scroll to property group menus

Additional Document Info

start page

  • 187

end page

  • 190

volume

  • 21

issue

  • 2

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support