<i>Streptomyces</i>
            Serine Protease (DHP-A) as a New Biocatalyst Capable of Forming Chiral Intermediates of 1,4-Dihydropyridine Calcium Antagonists

Arisawa, Akira; Matsufuji, Motoko; Nakashima, Takashi; Dobashi, Kazuyuki; Isshiki, Kunio; Yoshioka, Takeo; Yamada, Shigeru; Momose, Haruo; Taguchi, Seiichi

doi:10.1128/aem.68.6.2716-2725.2002

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…Actinomycetes are also common members of sponge-associated microbial communities and have been implicated as the producers of bioactive metabolites that were originally attributed to the host sponge (e.g., Hill et al 2003;Jiang et al 2008;Kim et al 2006). Thus, marine-derived actinomycetes are of growing biotechnological importance due to their vast metabolic capabilities, including the production of industrially applicable enzymes (Arisawa et al 2002;Eustaquio et al 2008;Ramesh and Mathivanan 2009;Schoemaker et al 2003;Zhang and Kim 2010) and of structurally unique and diverse bioactive secondary metabolites with anticancer, antiviral, antibacterial, and antimalarial activity (Fiedler et al 2005;Hill et al 2003;Kim et al 2006;Prudhomme et al 2008). One promising example that is currently in phase I clinical trials for various types of cancer is salinosporamide A, a cytotoxic proteasome inhibitor with antitumor and antimalarial activity isolated from a marine Salinispora species (Feling et al 2003;Fenical et al 2009;Prudhomme et al 2008).…”

Section: Introductionmentioning

confidence: 98%

Unique Actinomycetes from Marine Caves and Coral Reef Sediments Provide Novel PKS and NRPS Biosynthetic Gene Clusters

2011

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In the ever-expanding search for novel bioactive molecules and enzymes, marine actinomycetes have proven to be a productive source. While open reef sediment and sponge-associated actinomycetes have been extensively examined, their marine cave counterparts remain unevaluated. Anchialine cave systems in the Bahamas offered an ideal setting to evaluate the occurrence and variation within sediment-associated actinomycete communities. While in close geographical proximity to open reef environments, these systems provide a specialized environmental niche devoid of light and direct exposure to nutrient input. In the present study, selective isolation techniques and molecular methods were used to test the hypothesis that variable distribution of actinomycetes and secondary metabolite gene clusters occur between open reef and marine cave systems. The results indicated that differences exist within the culturable sediment-associated actinomycete communities between marine caves and open reef systems, with members of the genus Streptomyces dominating cultures from open reef sediments and a more diverse suite of actinomycetes isolated from marine cave sediment samples. Within the cave isolates, members of the proposed genus Solwaraspora were the most represented. Based on PKS- and NRPS-gene-targeted PCR amplification and sequencing, geographic variation in the occurrence of these biosynthetic pathways was also observed. These findings indicate that marine cave systems are a lucrative source in the search for novel secondary metabolite producers with biotechnological applications and that environmental and geographic factors likely affect the occurrence of these biosynthetic pathways.

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Section: Introductionmentioning

confidence: 98%

Unique Actinomycetes from Marine Caves and Coral Reef Sediments Provide Novel PKS and NRPS Biosynthetic Gene Clusters

2011

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“…Cloning and sequence analysis of the gene for DHP-A (dhpA) revealed that the enzyme was a serine protease that is highly similar in both structural and enzymatic features to SAM-P45. Homologous or heterologous expression of dhpA resulted in overproduction of the enzyme in culture supernatants, with 2.4-to 4.2-fold higher specific activities than in the parent S. viridosporus A-914 (90).…”

Section: Asymmetric Hydrolysis Of 14-dihydropyridine Diestersmentioning

confidence: 99%

“…Streptomyces viridosporus A-914 was screened as a producer of an enzyme that effectively forms chiral intermediates of 1,4-dihydropyridine calcium antagonists (90). The supernatant liquid of the growing culture of this strain exhibited high activity for enantioselective hydrolysis of prochiral 1,4-dihydropyridine diesters to the corresponding (4R) half esters.…”

Section: Asymmetric Hydrolysis Of 14-dihydropyridine Diestersmentioning

confidence: 99%

“…Enzymatic protection and de-protection under mild conditions have been demonstrated previously. Penicillin G amidase and phthalyl amidase have been used for the enzymatic de-protection of the phenylacetyl and phthaloyl groups from the corresponding amido or imido compounds (90,91). Acylases have been used widely in the enantioselective de-protection of N-acetyl-DL-amino acids (92).…”

Section: Enantioselective Enzymatic Cleavage Of the Carbobenzyloxy (Cmentioning

confidence: 99%

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Biocatalytic Synthesis of Chiral Pharmaceutical Intermediates

Patel

2005

ChemInform

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SummaryThe production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. Chiral intermediates and fine chemicals are in high demand from both the pharmaceutical and agrochemical industries for the preparation of bulk drug substances and agricultural products. The enormous potential of microorganisms and enzymes for the transformation of synthetic chemicals with high chemo-, regio-and enantioselectivities has been demonstrated. In this article, biocatalytic processes are described for the synthesis of chiral pharmaceutical intermediates.

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Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols

McConnell¹,

He²,

Nogle³

et al. 2007

Chirality

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Phenylglycidols substituted in the 2-, 3-, and 4- positions with fluorine, chlorine, and trifluoromethyl, and with methoxy in the 3- position, were synthesized from the corresponding E-cinnamic acids and separated into their (R,R)- and (S,S)- enantiomers using subcritical fluid chromatography with mixtures of MeOH in CO(2), on either a Chiralpak AD or AS chiral stationary phase. These compounds and commercially-available (R,R)- and (S,S)-phenylglycidol were analyzed for their vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotation (OR) properties to exemplify a strategy whereby the absolute stereochemistry of common and key chiral intermediates is established early in the structure-activity and structure-property relationship phase of a drug discovery program in a pharmaceutical company. From this study, substituents in the phenyl group of the synthesized molecules were found not to grossly alter spectroscopic features, and therefore, diagnostic absorption bands in the respective VCD spectra, and the sign and shape of the measured ECD curves could be used to determine and track the absolute stereochemistry of analogs without necessarily requiring time-consuming ab initio calculations of all low energy conformers for all compounds. VCD, OR, and ECD calculations for the determination of absolute configuration carried out at the DFT level with the hybrid B3PW91 functional and the TZVP basis set were found to be especially useful in this study.

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Streptomyces Serine Protease (DHP-A) as a New Biocatalyst Capable of Forming Chiral Intermediates of 1,4-Dihydropyridine Calcium Antagonists

Abstract: Streptomyces viridosporus

Cited by 7 publications

References 27 publications

Unique Actinomycetes from Marine Caves and Coral Reef Sediments Provide Novel PKS and NRPS Biosynthetic Gene Clusters

Unique Actinomycetes from Marine Caves and Coral Reef Sediments Provide Novel PKS and NRPS Biosynthetic Gene Clusters

Biocatalytic Synthesis of Chiral Pharmaceutical Intermediates

Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols

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