Combinatorial Biosynthesis of Sulfated Benzenediol Lactones with a Phenolic Sulfotransferase from Fusarium graminearum PH-1

Xie, Linan; Xiao, Dongliang; Wang, Xiaojing; Wang, Chen; Bai, Jing; Yue, Qun; Yue, Haitao; Li, Ye; Molnár, István; Xu, Yuquan; Zhang, Liwen

doi:10.1128/msphere.00949-20

Title: Combinatorial Biosynthesis of Sulfated Benzenediol Lactones with a Phenolic Sulfotransferase from Fusarium graminearum PH-1

Journal Article · Wed Nov 25 00:00:00 EST 2020 · mSphere

DOI:https://doi.org/10.1128/msphere.00949-20· OSTI ID:1817078

Xie, Linan ^[1]; Xiao, Dongliang ^[1]; Wang, Xiaojing ^[2]; Wang, Chen ^[1]; Bai, Jing ^[3]; Yue, Qun ^[1]; Yue, Haitao ^[4]; Li, Ye ^[5];

^[6]; Xu, Yuquan ^[1];

^[1]

Chinese Academy of Agricultural Sciences, Beijing (China)
Univ. of Arizona, Tucson, AZ (United States); Shanghai University of Medicine and Health Sciences (China)
Chinese Academy of Agricultural Sciences, Beijing (China); Suzhou Univ. of Science and Technology (China)
Xinjiang Univ., Urumqi (China)
Univ. of Arizona, Tucson, AZ (United States); Jiangnan Univ., Wuxi (China)
Univ. of Arizona, Tucson, AZ (United States)

Total biosynthesis or whole-cell biocatalytic production of sulfated small molecules relies on the discovery and implementation of appropriate sulfotransferase enzymes. Although fungi are prominent biocatalysts and have been used to sulfate drug-like phenolics, no gene encoding a sulfotransferase enzyme has been functionally characterized from these organisms. Here, we identify a phenolic sulfotransferase, FgSULT1, by genome mining from the plant-pathogenic fungus Fusarium graminearum PH-1. We expressed FgSULT1 in a Saccharomyces cerevisiae chassis to modify a broad range of benzenediol lactones and their nonmacrocyclic congeners, together with an anthraquinone, with the resulting unnatural natural product (uNP) sulfates displaying increased solubility. FgSULT1 shares low similarity with known animal and plant sulfotransferases. Instead, it forms a sulfotransferase family with putative bacterial and fungal enzymes for phase II detoxification of xenobiotics and allelochemicals. Among fungi, putative FgSULT1 homologues are encoded in the genomes of Fusarium spp. and a few other genera in nonsyntenic regions, some of which may be related to catabolic sulfur recycling. Computational structure modeling combined with site-directed mutagenesis revealed that FgSULT1 retains the key catalytic residues and the typical fold of characterized animal and plant sulfotransferases. Our work opens the way for the discovery of hitherto unknown fungal sulfotransferases and provides a synthetic biological and enzymatic platform that can be adapted to produce bioactive sulfates, together with sulfate ester standards and probes for masked mycotoxins, precarcinogenic toxins, and xenobiotics.

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Research Organization:: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1817078

Journal Information:: mSphere, Vol. 5, Issue 6; ISSN 2379-5042

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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Title: Combinatorial Biosynthesis of Sulfated Benzenediol Lactones with a Phenolic Sulfotransferase from Fusarium graminearum PH-1

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