Fungal indole alkaloid biogenesis through evolution of a bifunctional reductase/Diels–Alderase

Prenylated indole alkaloids such as the calmodulin-inhibitory malbrancheamides and anthelmintic paraherquamides possess great structural diversity and pharmaceutical utility. Here, we report complete elucidation of the malbrancheamide biosynthetic pathway accomplished through complementary approache...

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Veröffentlicht in:	Nature chemistry 2019-11, Vol.11 (11), p.972-980
Hauptverfasser:	Dan, Qingyun, Newmister, Sean A., Klas, Kimberly R., Fraley, Amy E., McAfoos, Timothy J., Somoza, Amber D., Sunderhaus, James D., Ye, Ying, Shende, Vikram V., Yu, Fengan, Sanders, Jacob N., Brown, W. Clay, Zhao, Le, Paton, Robert S., Houk, K. N., Smith, Janet L., Sherman, David H., Williams, Robert M.
Format:	Artikel
Sprache:	eng
Schlagworte:	631/45/535/1266 631/92/173 639/638/309/606 639/638/549/974 639/638/60 Alkaloids Analytical Chemistry Anthelmintic agents Antiparasitic agents Ascomycota - chemistry Biocatalysis Biochemistry Biomimetic synthesis Biomimetics Biosynthesis Calcium-binding protein Calmodulin Cascade chemical reactions Chemistry Chemistry and Materials Science Chemistry/Food Science computational chemistry Crystal structure Cycloaddition Cycloaddition Reaction Enantiomers enzyme mechanisms Enzymes Evolution Homology Indole Alkaloids - chemistry Indole Alkaloids - metabolism Indoles Inorganic Chemistry INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY Intermediates Metabolites Models, Molecular Molecular dynamics Molecular Structure NADP Natural products Organic Chemistry Oxidoreductases - metabolism Peptides Physical Chemistry Reductase Reductases Secondary metabolites Site-directed mutagenesis Substrates x-ray crystallography
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