Abstract
A new reduced hydroxamate, 2,3-dihydrotrichostatin A, was created from trichostatin A by employing a recombinant strain of Streptomyces venezuelae as a microbial catalyst. Compared with trichostatin A, 2,3-dihydrotrichostatin A showed similar antifungal activity against Saccharomyces cerevisiae, but, interestingly, approximately twice the cytostatic activity against human small-cell lung cancer cells. The production of 2,3-dihydrotrichostatin A via microbial biotransformation demonstrates that the regiospecific and substrate-flexible hydrogenation by S. venezuelae provides a new approach for creating natural product analogues with improved bioactive properties.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Biological Products / chemical synthesis
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Biological Products / chemistry
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Biological Products / pharmacology*
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Drug Screening Assays, Antitumor
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Genetic Engineering
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Humans
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Hydroxamic Acids / chemical synthesis
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology*
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Molecular Structure
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Saccharomyces cerevisiae / drug effects*
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Streptomyces / chemistry
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Streptomyces / genetics*
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Streptomyces / metabolism
Substances
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2,3-dihydrotrichostatin A
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Antifungal Agents
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Antineoplastic Agents
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Biological Products
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Hydroxamic Acids
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trichostatin A