Biosynthetic studies of terpentecin.

Isshiki, Kunio; Tamamura, Tsuyoshi; Sawa, Tsutomu; Naganawa, Hiroshi; Takeuchi, Tomio; Umezawa, Hamao

doi:10.7164/antibiotics.39.1634

Cited by 41 publications

(23 citation statements)

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“…Although most Streptomyces strains, which are prokaryotic, possess only the MEP pathway for the formation of IPP, it was previously clarified that both the MV and MEP pathways were operating in some Streptomyces strains such as Kitasatospora griseola (TP producer) [63], Actinoplanes sp. strain A40644 (BE-40644 producer) [64], Streptomyces sp.…”

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

confidence: 99%

“…4A) producer, was selected as the target because we also wanted to clone a diterpene cyclase gene responsible for the biosynthesis of TP in addition to the MV pathway genes was essential. Since TP possesses antibacterial activity [12] and has been shown to be mainly synthesized via the MV pathway [63], we expected that the MV pathway defective mutants would be present in TP non-producers, which could be easily detected by a bioassay. By treating the spores of the TP producer with a mutagen, we isolated a mutant lacking an HMG-CoA reductase activity as expected [71].…”

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: 99%

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

confidence: 99%

Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes

Dairi

2005

J Antibiot

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“…Thus, the assignments of 12-Hax, 13-Hax and 14-Hax were rigorously established for stereochemical analysis. In the ROESY spectrum of C, ROEs were observed between 17-CH 3 and 16-CH 3 and between 17-CH 3 and 13-Hax. Based on these results, the stereochemistries of 16-CH 3 and 17-CH 3 were determined to be axial as shown in Fig.…”

Section: Studies On Terpenoids Produced By Actinomycetesmentioning

confidence: 99%

“…2) and C which revealed migration of the double bond at C-10-C-11 in naphterpin to C-9-C-10 in B and C together with the appearance of a quaternary oxygenated carbon in B and C. Other moieties of these molecules remained unchanged suggesting that B and C were stereoisomers to each other at C-11. In order to determine the stereochemistry at C-11, we planned to utilize NOEs observed with16-CH 3 . Obstacle for these experiments, however, was severe overlapping of several protons from C-12 to C-14.…”

Section: Studies On Terpenoids Produced By Actinomycetesmentioning

confidence: 99%

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Studies on Terpenoids Produced by Actinomycetes

et al. 2005

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As a result of screening for terpenoids produced by Actinomycetes, naphterpins B and C, two new congeners of naphterpin were isolated from Streptomyces sp. CL190 and their structures were determined by NMR spectral analysis. We were interested in this phenomenon and initiated a screen for terpenoids of actinomycete origin. As a first step we examined in detail the minor metabolites of a naphterpin producer, Streptomyces sp. CL190 [7], with the aim of isolating new terpenoids from this organism.Since most terpenoids are hydrophobic in nature, we examined lipophilic fraction of the fermentation broth of Streptomyces sp. CL190 by TLC, and fractions positive to vanillin-H 2 SO 4 color reaction were analyzed by 1 H-NMR.Fractions showing sharp methyl singlet signals were judged to contain terpenoids and subjected to further purification. As a result, we succeeded in isolating two terpenoids, naphterpins B and C from Streptomyces sp. CL-190. We report herein their structures and biological activities.Streptomyces sp. CL-190 was cultivated in 15 ml test tubes each containing 5 ml of PC-1 medium (starch 1%, polypepton 1%, meat extract 1% and molasses 1%, pH 7.2 before sterilization) 28°C for two days. Each one ml of the broth was transferred to 500 ml baffled Erlenmeyer flasks containing 100 ml of K-medium (starch 2.5%, soybean meal 1.5%, dry yeast 0.2% and CaCO 3 0.4%, pH 6.2 before sterilization) and cultivated on a rotary shaker at 28°C for 6 days. The fermentation broth was filtered and the filtrate was extracted with AcOEt. The mycelium was extracted with acetone and after removal of the acetone, the aqueous residue was extracted with AcOEt. Both solvent extracts were combined and concentrated in vacuo to give an oily residue which was subjected to flash column chromatography (silica gel column, 25ϫ480 mm, equilibrated with hexane : AcOEtϭ4 : 1). After washing the column with the same solvent, the column was eluted with 200 ml of CHCl 3 : MeOHϭ20 : 1. This fraction was concentrated under reduced pressure and the residue was purified by preparative TLC (Merck silica gel 60 F 254 , 20ϫ 20 cm) developed with a solvent (CHCl 3 : MeOHϭ20 : 1). Two yellow bands (Rfϭ0.31 and 0.28) were separately scraped off and eluted with AcOEt to give crude samples that were named naphterpin B and naphterpin C. Each

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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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Biosynthetic studies of terpentecin.

Cited by 41 publications

References 4 publications

Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes

Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes

Studies on Terpenoids Produced by Actinomycetes

Diterpenoids from Streptomyces: Structures, Biosyntheses and Bioactivities

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