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A relationship between the mevalonate pathway and isoprenoid production in actinomycetes

Takashi Kawasaki1, Tomohisa Kuzuyama, Kazuo Furihata

  • 1Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan.

The Journal of Antibiotics
|February 7, 2004
PubMed

Insights

Many Streptomyces use the MEP pathway, but some employ the mevalonate pathway for terpenoid antibiotics. This study found clustered mevalonate and isoprenoid biosynthesis genes in Actinoplanes sp., suggesting the mevalonate pathway is a landmark for identifying isoprenoid compound producers.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Most Streptomyces utilize the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isopentenyl diphosphate production.
  • Some Streptomyces strains possess the mevalonate pathway, enabling the synthesis of terpenoid antibiotics.
  • Previous research indicated gene clusters for terpentecin biosynthesis are adjacent to mevalonate pathway genes.

Purpose of the Study:

  • To investigate the co-localization of mevalonate pathway genes and isoprenoid antibiotic biosynthetic genes in Actinoplanes sp. strain A40644.
  • To identify and confirm the function of genes involved in the biosynthesis of isoprenoid antibiotic BE-40644.

Main Methods:

  • Cloning of the mevalonate pathway gene cluster from Actinoplanes sp. strain A40644.
  • Sequencing of flanking regions to identify potential biosynthetic gene clusters.
  • Heterologous expression of a DNA fragment to confirm gene function.

Main Results:

  • A probable BE-40644 biosynthetic gene cluster was identified downstream of the mevalonate pathway gene cluster.
  • Heterologous expression confirmed that a 9-kb fragment contained genes essential for BE-40644 biosynthesis.
  • The study demonstrated co-localization of the mevalonate pathway and isoprenoid biosynthetic genes.

Conclusions:

  • The mevalonate pathway in actinomycetes is often clustered with genes responsible for isoprenoid compound biosynthesis.
  • The presence of the mevalonate pathway can serve as a reliable indicator for detecting isoprenoid compound production in actinomycetes.
  • This finding facilitates the discovery of novel bioactive compounds from microbial sources.

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