Discovery and Biosynthesis of Tetrachlorizine Reveals Enzymatic Benzylic Dehydrogenation via an ortho -Quinone Methide
2021
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Zugriff:
Ortho -quinone methides ( o -QMs) are reactive intermediates in biosynthesis that give rise to a variety of intra- and intermolecular cyclization/addition products in bacteria, fungi, and plants. Herein, we report a new metabolic deviation of an o -QM intermediate in a benzylic dehydrogenation reaction that links the newly described marine bacterial natural products dihydrotetrachlorizine and tetrachlorizine. We discovered these novel dichloropyrrole-containing compounds from actinomycete strain AJS-327 that unexpectedly harbors in its genome a biosynthetic gene cluster (BGC) of striking similarity to that of chlorizidine, another marine alkaloid bearing a different carbon skeleton. Heterologous expression of the homologous flavin-dependent oxidoreductase enzymes Tcz9 and Clz9 revealed their native functions in tetrachlorizine and chlorizidine biosynthesis, respectively, supporting divergent oxidative dehydrogenation and pyrrolizine-forming reactions. Swapping these berberine bridge enzyme-like oxidoreductases, we produced cyclized and dehydrogenated analogs of tetrachlorizine and chlorizidine, including a dearomatized chlorizidine analog that stabilizes an o -QM via conjugation with a 3 H -pyrrolizine ring.
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Discovery and Biosynthesis of Tetrachlorizine Reveals Enzymatic Benzylic Dehydrogenation via an ortho -Quinone Methide
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Autor/in / Beteiligte Person: | Trevor N. Purdy (10223921) ; Min Cheol Kim (271163) ; Reiko Cullum (7110245) ; William Fenical (48035) ; Bradley S. Moore (1331865) |
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Veröffentlichung: | 2021 |
Medientyp: | unknown |
DOI: | 10.1021/jacs.0c12415.s002 |
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