Cloning of a Gene Cluster Encoding Enzymes Responsible for the Mevalonate Pathway from a Terpenoid-antibiotic-producing Streptomyces Strain

Hamano, Yoshimitsu; Dairi, Tohru; Yamamoto, Masahiro; Kawasaki, Takashi; Kaneda, Kazuhide; Kuzuyama, Tomohisa; Itoh, Nobuhide; Seto, Haruo

doi:10.1271/bbb.65.1627

Cited by 39 publications

(42 citation statements)

References 39 publications

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“…Finally, we identified genes similar to those found in the strain CL190, in the same order [74]. However, in the TP producer, a GGDP (C 20 ) synthase gene was located just upstream of the MV pathway gene cluster [74] (Fig. 5A).…”

Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 59%

“…Therefore, the flanking regions of the HMG-CoA reductase gene cloned from the TP producer were also analyzed in order to investigate whether other MV pathway genes existed in a manner similar to that in strain CL190. Finally, we identified genes similar to those found in the strain CL190, in the same order [74]. However, in the TP producer, a GGDP (C 20 ) synthase gene was located just upstream of the MV pathway gene cluster [74] (Fig.…”

Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 61%

“…The MV pathway gene cluster thus obtained was confirmed to encode the predicted enzymes by heterologous expression in S. lividans and E. coli [74], which utilize only the MEP pathway for the formation of IPP. Moreover, the ORF2 and the ORF4 (Fig.…”

Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 90%

“…Moreover, the ORF2 and the ORF4 (Fig. 5A) were expressed as recombinant enzymes in E. coli, and an in vitro assay was performed because both the ORFs showed significant similarities to MK [74]. Considering the established MV pathway, one would be an MK, while the other would be a PMK, respectively.…”

Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 99%

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Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes

Dairi

2005

J Antibiot

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Most Streptomyces strains are equipped with only the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the formation of isopentenyl diphosphate, a common precursor of isoprenoids. In addition to this pathway, some Streptomyces strains possess the mevalonate (MV) pathway via which isoprenoid antibiotics are produced. We have recently cloned and analyzed the MV pathway gene clusters and their flanking regions from terpentecin, BE-40644, and furaquinocin A producers. All these clusters contained genes coding for mevalonate kinase, mevalonate diphosphate decarboxylase, phosphomevalonate kinase, type 2 IPP isomerase, HMGCoA reductase, and HMG-CoA synthase. The order of each of the open reading frames (ORFs) is also the same, and the respective homologous ORFs show more than 70% amino acid identity with each other. In contrast to these conservative gene organizations, the biosynthetic genes of terpentecin, BE-40644, and furaquinocin A were located just upstream and/or downstream of the MV pathway gene cluster. These facts suggested that all the actinomycete strains possessing both the MV and MEP pathways produce isoprenoid compounds and the biosynthetic genes of one of these isoprenoids usually exist adjacent to the MV pathway gene cluster. Therefore, when the presence of the MV cluster is detected by molecular genetic techniques, isoprenoids may be produced by the cultivation of these actinomycete strains. During the course of these studies, we identified diterpene cyclases possessing unique primary structures that differ from those of eukaryotes and catalyze unique reactions.Keywords isoprenoid, mevalonate pathway, biosynthesis, cyclase, Actinomycetes IntroductionActinomycete strains usually produce a number of secondary metabolites that often possess pharmaceutical activities. Therefore, for a long time, the strains have been used for many screenings to find novel, medically useful compounds. Consequently, more than 60 percent of the known antibiotics, including not only antibacterial antibiotics but also bioactive microbial compounds, have been reported to be produced by actinomycetes [1]. Presently, such pharmaceutically important, novel compounds can be found in the culture broth of actinomycete strains by screening rare actinomycetes, developing new screening strategies, employing sensitive assay methods for the detection of low concentrations of antibiotics, etc. However, sometimes, "semi-new antibiotics"-derivatives of known antibiotics-were isolated; discovering novel antibiotics every year became very difficult.In the past two decades, recombinant DNA technology has come into play in this field. Gene clusters encoding many natural products have been cloned and characterized. Moreover, whole-genome sequencing has uncovered hundreds of candidates for secondary metabolic pathways. Among them, the biosynthetic machinery of nonribosomal peptide and polyketide natural products has been extensively investigated [2ϳ7]. Recent progress in the application of combinatorial biosynthesis methods to these bi...

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Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 59%

Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 61%

Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 90%

Section: Cloning and Analysis Of A Mevalonate Pathway Gene Cluster Frmentioning

confidence: 99%

See 2 more Smart Citations

Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes

Dairi

2005

J Antibiot

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“…1). [32][33][34] Therefore, our attention was then directed to cloning of genes responsible for the nonmevalonate pathway from strain MF730-N6. In this study, we report cloning of two distinct dxs genes (dxs 1 and dxs 2), a dxr gene, and a gap gene from strain MF730-N6.…”

Section: )mentioning

confidence: 99%

Growth-phase Dependent Expression of the Mevalonate Pathway in a Terpenoid Antibiotic-producingStreptomycesStrain

Hamano

Dairi

Yamamoto

et al. 2002

Bioscience, Biotechnology, and Biochemistry

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Diterpenoids from Streptomyces: Structures, Biosyntheses and Bioactivities

Gong

Yong

et al. 2022

ChemBioChem

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Bacteria, especially Streptomyces spp., have emerged as a rich source for natural diterpenoids with diverse structures and broad bioactivities. Here, we review diterpenoids biosynthesized by Streptomyces, with an emphasis on their structures, biosyntheses, and bioactivities. Although diterpenoids from Streptomyces are relatively rare compared to those from plants and fungi, their novel skeletons, biosyntheses and bioactivities present opportunities for discovering new drugs, enzyme mechanisms, and applications in biocatalysis and metabolic pathway engineering.

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Cloning of a Gene Cluster Encoding Enzymes Responsible for the Mevalonate Pathway from a Terpenoid-antibiotic-producing Streptomyces Strain

Cited by 39 publications

References 39 publications

Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes

Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes

Growth-phase Dependent Expression of the Mevalonate Pathway in a Terpenoid Antibiotic-producingStreptomycesStrain

Diterpenoids from Streptomyces: Structures, Biosyntheses and Bioactivities

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