Structural basis for divergent C–H hydroxylation selectivity in two Rieske oxygenases

Lukowski, April L.; Liu, Jianxin; Bridwell-Rabb, Jennifer; Narayan, Alison R.  H.

doi:10.1038/s41467-020-16729-0

Title: Structural basis for divergent C–H hydroxylation selectivity in two Rieske oxygenases

Journal Article · 11 June 2020 · Nature Communications

DOI: https://doi.org/10.1038/s41467-020-16729-0 · OSTI ID:1633803

Lukowski, April L. ^[1];

^[1];

^[1]

Univ. of Michigan, Ann Arbor, MI (United States)

Biocatalysts that perform C–H hydroxylation exhibit exceptional substrate specificity and site-selectivity, often through the use of high valent oxidants to activate these inert bonds. Rieske oxygenases are examples of enzymes with the ability to perform precise mono- or dioxygenation reactions on a variety of substrates. Understanding the structural features of Rieske oxygenases responsible for control over selectivity is essential to enable the development of this class of enzymes for biocatalytic applications. Decades of research has illuminated the critical features common to Rieske oxygenases, however, structural information for enzymes that functionalize diverse scaffolds is limited. Here, we report the structures of two Rieske monooxygenases involved in the biosynthesis of paralytic shellfish toxins (PSTs), SxtT and GxtA, adding to the short list of structurally characterized Rieske oxygenases. Based on these structures, substrate-bound structures, and mutagenesis experiments, we implicate specific residues in substrate positioning and the divergent reaction selectivity observed in these two enzymes.

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Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: NIH; USDOE

OSTI ID:: 1633803

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 11; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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