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Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.

07:00 EST 8th November 2019 | BioPortfolio

Summary of "Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis."

MtmOIV and MtmW catalyze the final two reactions in the mithramycin (MTM) biosynthetic pathway, the Baeyer-Villiger opening of the fourth ring of premithramycin B (PMB), creating the C3 pentyl side chain, strictly followed by reduction of the distal keto group on the new side chain. Unexpectedly this results in a C2 stereoisomer of mithramycin, iso-mithramycin (iso-MTM). Iso-MTM undergoes a non-enzymatic isomerization to MTM catalyzed by Mg2+ ions. Crystal structures of MtmW and its complexes with co-substrate NADPH and PEG, suggest a catalytic mechanism of MtmW. The structures also show that a tetrameric assembly of this enzyme strikingly resembles of the ring-shaped β subunit of a vertebrate ion channel. We show that MtmW and MmOIV form a complex in the presence of PMB and NADPH, presumably to hand over the unstable MtmOIV product to MtmW, yielding iso-MTM, as a potential self-resistance mechanism against MTM toxicity.

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This article was published in the following journal.

Name: Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
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