Nonspecific Heme-Binding Cyclase, AbmU, Catalyzes [4 + 2] Cycloaddition during Neoabyssomicin Biosynthesis.

ABSTRACT: Diels-Alder (DA) [4 + 2]-cycloaddition reactions rank among the most powerful transformations in synthetic organic chemistry; biosynthetic examples, however, are few and far between. We report here a heme-binding cyclase, AbmU, that catalyzes an essential [4 + 2] cycloaddition during neoabyssomicin scaffold assembly. In vivo genetic and in vitro biochemical analyses strongly suggest that AbmU catalyzes an intramolecular and stereoselective [4 + 2] cycloaddition to form a spirotetronate skeleton from an acyclic substrate featuring both a terminal 1,3-diene and an exo-methylene group. Biochemical assays and X-ray diffraction analyses reveal that AbmU binds nonspecifically to a heme b cofactor and that this association does not play a catalytic role in AbmU catalysis. A detailed study

SUBMITTER: Li Q 

PROVIDER: S-EPMC7439702 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature