Investigation of 2,2′-Bipyridine Biosynthesis Reveals a Common Two-Component System for Aldehydes Production by Carboxylate Reduction

Here, we report a two-component enzymatic system that efficiently catalyzes the reduction of a carboxylate to an aldehyde in the biosynthesis of 2,2′-bipyridine antibiotics caerulomycins. The associated paradigm involves the activation of carboxylate by ATP-dependent adenylation protein CaeF, follow...

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Bibliographic Details
Published in:Organic letters 2022-01, Vol.24 (3), p.897-902
Main Authors: Chen, Ming, Pang, Bo, Ding, Wenping, Zhao, Qunfei, Tang, Zhijun, Liu, Wen
Format: Article
Language:English
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Summary:Here, we report a two-component enzymatic system that efficiently catalyzes the reduction of a carboxylate to an aldehyde in the biosynthesis of 2,2′-bipyridine antibiotics caerulomycins. The associated paradigm involves the activation of carboxylate by ATP-dependent adenylation protein CaeF, followed by its reduction catalyzed by CaeB2, a new class of NADPH-dependent aldehyde dehydrogenase (ALDH) that directly reduces AMP-conjugated carboxylate, which is distinct from the known aldehyde-producing enzymes that reduce ACP- or CoA-conjugated carboxylates.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.1c04239