Enzymatic Hydrolysis of Resorcylic Acid Lactones by an Sp

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2024 Sep 27

PMID 39330862

Authors

Shawn J Hoogstra

Kyle N Hendricks

David R McMullin

Justin B Renaud

Juhi Bora

Mark W Sumarah

Christopher P Garnham

Affiliations

Soon will be listed here.

Abstract

Zearalenone and radicicol are resorcylic acid lactones produced by numerous plant pathogenic fungi. Zearalenone is a non-steroidal estrogen mimic that can cause serious reproductive issues in livestock that consume contaminated feed. Radicicol is a potent inhibitor of the molecular chaperone Hsp90, which, in plants, has an important role in coordinating the host's immune response during infection. Here, we describe the identification and characterization of a soil-borne strain of the Gram-positive bacterium sp. capable of hydrolyzing the macrolide ring of resorcylic acid lactones, including zearalenone and radicicol. Proteomic analysis of biochemically enriched fractions from the isolated and cultured bacterium identified an α/β-hydrolase responsible for this activity. A recombinantly expressed and purified form of the hydrolase (termed RALH) was active against both zearalenone and radicicol. Interpretation of high-resolution mass spectrometry and NMR data confirmed the structures of the enzymatic products as the previously reported non-toxic metabolite hydrolyzed zearalenone and hydrolyzed radicicol. Hydrolyzed radicicol was demonstrated to no longer inhibit the ATPase activity of the Hsp90 homolog in vitro. Enzymatic degradation of resorcylic acid lactones will enable insight into their biological functions.

Citing Articles

The Protein Engineering of Zearalenone Hydrolase Results in a Shift in the pH Optimum of the Relative Activity of the Enzyme.

Dotsenko A, Sinelnikov I, Zorov I, Denisenko Y, Rozhkova A, Shcherbakova L Toxins (Basel). 2024; 16(12).

PMID: 39728798 PMC: 11679840. DOI: 10.3390/toxins16120540.

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