Microbial Synthesis of Purine Arabinosides and Their Biological Activity

Utagawa, Takashi; Morisawa, Hirokazu; Yamanaka, Shigeru; Yamazaki, Akihiro; Yoshinaga, Fumihiro; Hirose, Yoshio

doi:10.1080/00021369.1985.10867042

Cited by 5 publications

(5 citation statements)

References 1 publication

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“…Arabino- (17,20) and 2Ј-amino-2Ј-deoxyribonucleosides (38,39) have been obtained enzymatically in good yields, although the synthesis of 3Ј-amino-2Ј,3Ј-dideoxy-5-halouridine from 3Ј-amino-2Ј,3Ј-dideoxythymidine and the corresponding 5-halouracil in the presence of thymidine phosphorylase afforded very low yield (40). Zaitseva et al (41) have synthesized 3Ј-amino-2Ј,3Ј-dideoxyadenosine and 3Ј-amino-2Ј,3Ј-dideoxyguanosine from the corresponding thymidine or uracil as glycosyl donor and adenine or guanine, respectively, as acceptor in the presence of glutaraldehyde-treated cells of E. coli BM-11 in acceptable yields.…”

Section: Scheme 2 Schemementioning

confidence: 99%

Nucleoside Synthesis Mediated by Glycosyl Transferring Enzymes

Prasad

Trikha

Parmar

1999

Bioorganic Chemistry

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Section: Scheme 2 Schemementioning

confidence: 99%

Nucleoside Synthesis Mediated by Glycosyl Transferring Enzymes

Prasad

Trikha

Parmar

1999

Bioorganic Chemistry

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“…herpes simplex and varicella zoster viruses. 9 Famciclovir has been approved by the FDA for the treatment of herpes zoster (commonly known as shingles) and acute recurrent genital herpes. 10 The industrial production of purine analogues is usually through a dehydrazination reaction promoted by HgO (Scheme 1a).…”

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confidence: 99%

Efficient synthesis of nebularine and vidarabine via dehydrazination of (hetero)aromatics catalyzed by CuSO₄in water

et al. 2014

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A simple dehydrazination reaction has been achieved in the presence of a catalytic amount of CuSO 4 for the first time. With CuSO 4(2 mol%) as a catalyst and water as a solvent, the dehydrazination products were obtained in good yields (66-95%). Moreover, the drugs nebularine and vidarabine were afforded successfully, and vidarabine could be produced on a 0.923 kg scale, which shows good potential for industrial applications.

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“…Moreover, 2=-Cl PTN is able to greatly potentiate the antiviral efficacy of Ara-A, and the acute toxicity of 2=-Cl PTN in mice was less than that of coformycin and PTN (6). Regarding 2=-amino dA, it has been shown to be a selectively effective inhibitor against the replication of some riboviruses, including the measles virus (10,11). Very interestingly, two other related adenosine analogs designated 2=-amino-2=-deoxyguanosine (2=-amino dG) (12) and 3=-amino-3=-deoxyadenosine (3=-amino dA) (13) have been discovered prior to 2=-amino dA (Fig.…”

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confidence: 99%

Biosynthesis of 2′-Chloropentostatin and 2′-Amino-2′-Deoxyadenosine Highlights a Single Gene Cluster Responsible for Two Independent Pathways in Actinomadura sp. Strain ATCC 39365

Gao

et al. 2017

Appl Environ Microbiol

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2=-Chloropentostatin (2=-Cl PTN, 2=-chloro-2=-deoxycoformycin) and 2=-amino-2=-deoxyadenosine (2=-amino dA) are two adenosine-derived nucleoside antibiotics coproduced by Actinomadura sp. strain ATCC 39365. 2=-Cl PTN is a potent adenosine deaminase (ADA) inhibitor featuring an intriguing 1,3-diazepine ring, as well as a chlorination at C-2= of ribose, and 2=-amino dA is an adenosine analog showing bioactivity against RNA-type virus infection. However, the biosynthetic logic of them has remained poorly understood. Here, we report the identification of a single gene cluster (ada) essential for the biosynthesis of 2=-Cl PTN and 2=-amino dA. Further systematic genetic investigations suggest that 2=-Cl PTN and 2=-amino dA are biosynthesized by independent pathways. Moreover, we provide evidence that a predicted cation/H ϩ antiporter, AdaE, is involved in the chlorination step during 2=-Cl PTN biosynthesis. Notably, we demonstrate that 2=-amino dA biosynthesis is initiated by a Nudix hydrolase, AdaJ, catalyzing the hydrolysis of ATP. Finally, we reveal that the host ADA (designated ADA1), capable of converting adenosine/2=-amino dA to inosine/2=-amino dI, is not very sensitive to the powerful ADA inhibitor pentostatin. These findings provide a basis for the further rational pathway engineering of 2=-Cl PTN and 2=-amino dA production.IMPORTANCE 2=-Cl PTN/PTN and 2=-amino dA have captivated the great interests of scientists, owing to their unusual chemical structures and remarkable bioactivities. However, the precise logic for their biosynthesis has been elusive for decades. Actually, the identification and elucidation of their biosynthetic pathways not only enrich the biochemical repertoire of novel enzymatic reactions but may also lay solid foundations for the pathway engineering and combinatorial biosynthesis of this family of purine nucleoside antibiotics to generate novel hybrid analogs with improved features.KEYWORDS 2=-chloropentostatin, 2=-amino-2=-deoxyadenosine, nucleoside antibiotics, biosynthesis, Nudix hydrolase, adenosine deaminase N ucleoside antibiotics are a large family of important microbial natural products harboring wide-range biological properties and distinctive structural features (1-3). Their biosynthesis generally follows a succinct logic by sequential enzymatic modification of nucleosides or nucleotides originating from primary metabolisms (1). Usually, nucleosides and nucleotides play pleiotropic roles in most fundamental cellular metabolisms; therefore, nucleoside antibiotics are able to target the biosynthesis of diverse biomacromolecules, including nucleic acids, proteins, and glycans (1).

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Microbial Synthesis of Purine Arabinosides and Their Biological Activity

Cited by 5 publications

References 1 publication

Nucleoside Synthesis Mediated by Glycosyl Transferring Enzymes

Nucleoside Synthesis Mediated by Glycosyl Transferring Enzymes

Efficient synthesis of nebularine and vidarabine via dehydrazination of (hetero)aromatics catalyzed by CuSO₄in water

Biosynthesis of 2′-Chloropentostatin and 2′-Amino-2′-Deoxyadenosine Highlights a Single Gene Cluster Responsible for Two Independent Pathways in Actinomadura sp. Strain ATCC 39365

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Microbial Synthesis of Purine Arabinosides and Their Biological Activity

Cited by 5 publications

References 1 publication

Nucleoside Synthesis Mediated by Glycosyl Transferring Enzymes

Nucleoside Synthesis Mediated by Glycosyl Transferring Enzymes

Efficient synthesis of nebularine and vidarabine via dehydrazination of (hetero)aromatics catalyzed by CuSO4in water

Biosynthesis of 2′-Chloropentostatin and 2′-Amino-2′-Deoxyadenosine Highlights a Single Gene Cluster Responsible for Two Independent Pathways in Actinomadura sp. Strain ATCC 39365

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Efficient synthesis of nebularine and vidarabine via dehydrazination of (hetero)aromatics catalyzed by CuSO₄in water