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

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

Journal Article · Tue Nov 24 23:00:00 EST 2020 · mSphere

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

Xie, Linan ^[1]; Xiao, Dongliang ^[2]; Wang, Xiaojing ^[3]; Wang, Chen ^[2]; Bai, Jing ^[4]; Yue, Qun ^[2]; Yue, Haitao ^[5]; Li, Ye ^[6]; ^[7]; Xu, Yuquan ^[2]; ^[2]

Chinese Academy of Agricultural Sciences, Beijing (China); Edgewater Federal Solutions/OSTI
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.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1817078

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

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (64)

Sulfotransferases: Structure, Mechanism, Biological Activity, Inhibition, and Synthetic Utility Chapman, Eli; Best, Michael D.; Hanson, Sarah R. Angewandte Chemie International Edition, Vol. 43, Issue 27 https://doi.org/10.1002/anie.200300631	journal	July 2004
A microbial-enzymatic strategy for producing chondroitin sulfate glycosaminoglycans Zhou, Zhengxiong; Li, Qing; Huang, Hao Biotechnology and Bioengineering, Vol. 115, Issue 6 https://doi.org/10.1002/bit.26577	journal	March 2018
Crystal structures of human sulfotransferases SULT1B1 and SULT1C1 complexed with the cofactor product adenosine-3′- 5′-diphosphate (PAP) Dombrovski, Luidmila; Dong, Aiping; Bochkarev, Alexey Proteins: Structure, Function, and Bioinformatics, Vol. 64, Issue 4 https://doi.org/10.1002/prot.21048	journal	June 2006
Deoxynivalenol-sulfates: identification and quantification of novel conjugated (masked) mycotoxins in wheat Warth, Benedikt; Fruhmann, Philipp; Wiesenberger, Gerlinde Analytical and Bioanalytical Chemistry, Vol. 407, Issue 4 https://doi.org/10.1007/s00216-014-8340-4	journal	December 2014
Expression and secretion of glycosylated heparin biosynthetic enzymes using Komagataella pastoris Englaender, Jacob A.; Zhu, Yuanyuan; Shirke, Abhijit N. Applied Microbiology and Biotechnology, Vol. 101, Issue 7 https://doi.org/10.1007/s00253-016-8047-x	journal	December 2016
Expression of chondroitin-4-O-sulfotransferase in Escherichia coli and Pichia pastoris He, Wenqin; Zhu, Yuanyuan; Shirke, Abhijeet Applied Microbiology and Biotechnology, Vol. 101, Issue 18 https://doi.org/10.1007/s00253-017-8411-5	journal	July 2017
Chemoenzymatic synthesis of 3′-phosphoadenosine-5′-phosphosulfate coupling with an ATP regeneration system An, Cuiying; Zhao, Long; Wei, Zhaojun Applied Microbiology and Biotechnology, Vol. 101, Issue 20 https://doi.org/10.1007/s00253-017-8511-2	journal	September 2017
Whole-cell-dependent biosynthesis of sulfo-conjugate using human sulfotransferase expressing budding yeast Nishikawa, Miyu; Masuyama, Yuuka; Nunome, Motomichi Applied Microbiology and Biotechnology, Vol. 102, Issue 2 https://doi.org/10.1007/s00253-017-8621-x	journal	November 2017
Enzymatic and non-enzymatic sulfation mechanisms in the biological actions of minoxidil Meisheri, Kaushik D.; Johnson, Garland A.; Puddington, Lynn Biochemical Pharmacology, Vol. 45, Issue 2 https://doi.org/10.1016/0006-2952(93)90061-Z	journal	January 1993
The dimerization motif of cytosolic sulfotransferases Petrotchenko, Evgeniy V.; Pedersen, Lars C.; Borchers, Christoph H. FEBS Letters, Vol. 490, Issue 1-2 https://doi.org/10.1016/S0014-5793(01)02129-9	journal	February 2001
Function and organization of the human cytosolic sulfotransferase (SULT) family Coughtrie, Michael W. H. Chemico-Biological Interactions, Vol. 259 https://doi.org/10.1016/j.cbi.2016.05.005	journal	November 2016
Biosynthesis of Sulfated Glycopeptide Antibiotics by Using the Sulfotransferase StaL Lamb, Sherry S.; Patel, Tejal; Koteva, Kalinka P. Chemistry & Biology, Vol. 13, Issue 2 https://doi.org/10.1016/j.chembiol.2005.12.003	journal	February 2006
Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii Wang, Shuhao; Xu, Yuquan; Maine, Erin A. Chemistry & Biology, Vol. 15, Issue 12 https://doi.org/10.1016/j.chembiol.2008.10.006	journal	December 2008
Structural plasticity in the human cytosolic sulfotransferase dimer and its role in substrate selectivity and catalysis Tibbs, Zachary E.; Rohn-Glowacki, Katie Jo; Crittenden, Frank Drug Metabolism and Pharmacokinetics, Vol. 30, Issue 1 https://doi.org/10.1016/j.dmpk.2014.10.004	journal	February 2015
Benzenediol lactones: a class of fungal metabolites with diverse structural features and biological activities Shen, Weiyun; Mao, Hongqiang; Huang, Qian European Journal of Medicinal Chemistry, Vol. 97 https://doi.org/10.1016/j.ejmech.2014.11.067	journal	June 2015
Profiling and identification of the metabolites of baicalin and study on their tissue distribution in rats by ultra-high-performance liquid chromatography with linear ion trap-Orbitrap mass spectrometer Zhang, Jiayu; Cai, Wei; Zhou, Yuan Journal of Chromatography B, Vol. 985 https://doi.org/10.1016/j.jchromb.2015.01.018	journal	March 2015
Sulfotransferase 1A1 Substrate Selectivity: A Molecular Clamp Mechanism Cook, Ian; Wang, Ting; Leyh, Thomas S. Biochemistry, Vol. 54, Issue 39 https://doi.org/10.1021/acs.biochem.5b00406	journal	September 2015
Chlorinated Dehydrocurvularins and Alterperylenepoxide A fromAlternariasp. AST0039, a Fungal Endophyte ofAstragalus lentiginosus Bashyal, Bharat P.; Wijeratne, E. M. Kithsiri; Tillotson, Joseph Journal of Natural Products, Vol. 80, Issue 2 https://doi.org/10.1021/acs.jnatprod.6b00960	journal	January 2017
Diversity-Oriented Combinatorial Biosynthesis of Hybrid Polyketide Scaffolds from Azaphilone and Benzenediol Lactone Biosynthons Bai, Jing; Lu, Yuanyuan; Xu, Ya-ming Organic Letters, Vol. 18, Issue 6 https://doi.org/10.1021/acs.orglett.6b00110	journal	March 2016
Insights into the Biosynthesis of 12-Membered Resorcylic Acid Lactones from Heterologous Production in Saccharomyces cerevisiae Xu, Yuquan; Zhou, Tong; Espinosa-Artiles, Patricia ACS Chemical Biology, Vol. 9, Issue 5 https://doi.org/10.1021/cb500043g	journal	March 2014
Thioesterase Domains of Fungal Nonreducing Polyketide Synthases Act as Decision Gates during Combinatorial Biosynthesis Xu, Yuquan; Zhou, Tong; Zhang, Shuwei Journal of the American Chemical Society, Vol. 135, Issue 29 https://doi.org/10.1021/ja4041362	journal	July 2013
Intrinsic and Extrinsic Programming of Product Chain Length and Release Mode in Fungal Collaborating Iterative Polyketide Synthases Wang, Chen; Wang, Xiaojing; Zhang, Liwen Journal of the American Chemical Society, Vol. 142, Issue 40 https://doi.org/10.1021/jacs.0c07050	journal	August 2020
Rational Reprogramming of O -Methylation Regioselectivity for Combinatorial Biosynthetic Tailoring of Benzenediol Lactone Scaffolds Wang, Xiaojing; Wang, Chen; Duan, Lixin Journal of the American Chemical Society, Vol. 141, Issue 10 https://doi.org/10.1021/jacs.8b12967	journal	February 2019
Regeneration of PAPS for the Enzymatic Synthesis of Sulfated Oligosaccharides Burkart, Michael D.; Izumi, Masayuki; Chapman, Eli The Journal of Organic Chemistry, Vol. 65, Issue 18 https://doi.org/10.1021/jo000266o	journal	August 2000
Microbial O-Demethylation, Hydroxylation, Sulfation, and Ribosylation of a Xanthone Derivative from Halenia elliptica Yuan, Wei; Zhang, Li-Ping; Cheng, Ke-Di Journal of Natural Products, Vol. 69, Issue 5 https://doi.org/10.1021/np050472x	journal	April 2006
Isolation of Psammaplin A 11‘-Sulfate and Bisaprasin 11‘-Sulfate from the Marine Sponge Aplysinella rhax Pham, Ngoc Bich; Butler, Mark S.; Quinn, Ronald J. Journal of Natural Products, Vol. 63, Issue 3 https://doi.org/10.1021/np990335y	journal	February 2000
Recent progress regarding the bioactivities, biosynthesis and synthesis of naturally occurring resorcinolic macrolides Xu, Jing; Jiang, Cheng-shi; Zhang, Zai-long Acta Pharmacologica Sinica, Vol. 35, Issue 3 https://doi.org/10.1038/aps.2013.155	journal	January 2014
I-TASSER: a unified platform for automated protein structure and function prediction Roy, Ambrish; Kucukural, Alper; Zhang, Yang Nature Protocols, Vol. 5, Issue 4 https://doi.org/10.1038/nprot.2010.5	journal	March 2010
The influence of drug-like concepts on decision-making in medicinal chemistry Leeson, Paul D.; Springthorpe, Brian Nature Reviews Drug Discovery, Vol. 6, Issue 11 https://doi.org/10.1038/nrd2445	journal	November 2007
Structural and biochemical studies of sulphotransferase 18 from Arabidopsis thaliana explain its substrate specificity and reaction mechanism Hirschmann, Felix; Krause, Florian; Baruch, Petra Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-04539-2	journal	June 2017
New insights into the echinocandins and other fungal non-ribosomal peptides and peptaibiotics Bills, Gerald; Li, Yan; Chen, Li Nat. Prod. Rep., Vol. 31, Issue 10 https://doi.org/10.1039/C4NP00046C	journal	January 2014
Selective inhibition of p97 by chlorinated analogues of dehydrocurvularin Tillotson, Joseph; Bashyal, Bharat P.; Kang, MinJin Organic & Biomolecular Chemistry, Vol. 14, Issue 25 https://doi.org/10.1039/C6OB00560H	journal	January 2016
A sulfated metabolite produced by stf3 negatively regulates the virulence of Mycobacterium tuberculosis Mougous, Joseph D.; Senaratne, Ryan H.; Petzold, Christopher J. Proceedings of the National Academy of Sciences, Vol. 103, Issue 11 https://doi.org/10.1073/pnas.0510861103	journal	March 2006
A structural and biochemical basis for PAPS-independent sulfuryl transfer by aryl sulfotransferase from uropathogenic Escherichia coli Malojčić, Goran; Owen, Robin L.; Grimshaw, John P. A. Proceedings of the National Academy of Sciences, Vol. 105, Issue 49 https://doi.org/10.1073/pnas.0806997105	journal	December 2008
Sulfonation of glycopeptide antibiotics by sulfotransferase StaL depends on conformational flexibility of aglycone scaffold Shi, Rong; Munger, Christine; Kalan, Lindsay Proceedings of the National Academy of Sciences, Vol. 109, Issue 29 https://doi.org/10.1073/pnas.1205377109	journal	July 2012
Rational reprogramming of fungal polyketide first-ring cyclization Xu, Yuquan; Zhou, Tong; Zhou, Zhengfu Proceedings of the National Academy of Sciences, Vol. 110, Issue 14 https://doi.org/10.1073/pnas.1301201110	journal	March 2013
Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases Xu, Yuquan; Zhou, Tong; Zhang, Shuwei Proceedings of the National Academy of Sciences, Vol. 111, Issue 34 https://doi.org/10.1073/pnas.1406999111	journal	July 2014
Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis Xie, Linan; Zhang, Liwen; Wang, Chen Proceedings of the National Academy of Sciences, Vol. 115, Issue 22 https://doi.org/10.1073/pnas.1716046115	journal	May 2018
The Sulfuryl Transfer Mechanism: CRYSTAL STRUCTURE OF A VANADATE COMPLEX OF ESTROGEN SULFOTRANSFERASE AND MUTATIONAL ANALYSIS Kakuta, Yoshimitsu; Petrotchenko, Evgeny V.; Pedersen, Lars C. Journal of Biological Chemistry, Vol. 273, Issue 42 https://doi.org/10.1074/jbc.273.42.27325	journal	October 1998
Structure of a Human Carcinogen-converting Enzyme, SULT1A1 Gamage, Niranjali U.; Duggleby, Ronald G.; Barnett, Amanda C. Journal of Biological Chemistry, Vol. 278, Issue 9 https://doi.org/10.1074/jbc.M207246200	journal	February 2003
Enzymatic aspects of the phenol (aryl) sulfotransferases^* Duffel, Michael W.; Marshall, A. David; McPhie, Peter Drug Metabolism Reviews, Vol. 33, Issue 3-4 https://doi.org/10.1081/DMR-120001394	journal	January 2001
MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) Software Version 4.0 Tamura, K.; Dudley, J.; Nei, M. Molecular Biology and Evolution, Vol. 24, Issue 8 https://doi.org/10.1093/molbev/msm092	journal	April 2007
MUSCLE: multiple sequence alignment with high accuracy and high throughput Edgar, R. C. Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797 https://doi.org/10.1093/nar/gkh340	journal	March 2004
Dali server update Holm, Liisa; Laakso, Laura M. Nucleic Acids Research, Vol. 44, Issue W1 https://doi.org/10.1093/nar/gkw357	journal	April 2016
Biotransformation of the mycotoxin zearalenone by fungi of the generaRhizopusandAspergillus Brodehl, Antje; Möller, Anne; Kunte, Hans-Jörg FEMS Microbiology Letters, Vol. 359, Issue 1 https://doi.org/10.1111/1574-6968.12586	journal	September 2014
Design and Interpretation of Human Sulfotransferase A1 Assays Wang, T.; Cook, I.; Leyh, T. S. Drug Metabolism and Disposition, Vol. 44, Issue 4 https://doi.org/10.1124/dmd.115.068205	journal	December 2015
Complete Reconstitution of a Highly Reducing Iterative Polyketide Synthase Ma, Suzanne M.; Li, Jesse W. -H.; Choi, Jin W. Science, Vol. 326, Issue 5952 https://doi.org/10.1126/science.1175602	journal	October 2009
Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats Schmitt-Hoffmann, Anne-Hortense; Kato, Kota; Townsend, Robert Antimicrobial Agents and Chemotherapy, Vol. 61, Issue 12 https://doi.org/10.1128/AAC.01292-17	journal	December 2017
Structural Requirements for the Activity of the MirB Ferrisiderophore Transporter of Aspergillus fumigatus Raymond-Bouchard, Isabelle; Carroll, Cassandra S.; Nesbitt, Jason R. Eukaryotic Cell, Vol. 11, Issue 11 https://doi.org/10.1128/EC.00159-12	journal	November 2012
Combinatorial Biosynthesis of Sulfated Benzenediol Lactones with a Phenolic Sulfotransferase from Fusarium graminearum PH-1 Xie, Linan; Xiao, Dongliang; Wang, Xiaojing mSphere, Vol. 5, Issue 6 https://doi.org/10.1128/mSphere.00949-20	journal	December 2020
The completed genome sequence of the pathogenic ascomycete fungus Fusarium graminearum King, Robert; Urban, Martin; Hammond-Kosack, Michael C. U. BMC Genomics, Vol. 16, Issue 1 https://doi.org/10.1186/s12864-015-1756-1	journal	July 2015
Whole genome sequencing and comparative genomics of closely related Fusarium Head Blight fungi: Fusarium graminearum, F. meridionale and F. asiaticum Walkowiak, Sean; Rowland, Owen; Rodrigue, Nicolas BMC Genomics, Vol. 17, Issue 1 https://doi.org/10.1186/s12864-016-3371-1	journal	December 2016
Total Biosynthesis of Diterpene Aphidicolin, a Specific Inhibitor of DNA Polymerase α: Heterologous Expression of Four Biosynthetic Genes inAspergillus oryzae Fujii, Ryuya; Minami, Atsushi; Tsukagoshi, Tae Bioscience, Biotechnology, and Biochemistry, Vol. 75, Issue 9 https://doi.org/10.1271/bbb.110366	journal	September 2011
Discovery of micafungin (FK463): A novel antifungal drug derived from a natural product lead Fujie, Akihiko Pure and Applied Chemistry, Vol. 79, Issue 4 https://doi.org/10.1351/pac200779040603	journal	January 2007
Mechanism of sulfotransferase pharmacogenetics in altered xenobiotic metabolism Chen, Bo-Han; Wang, Chen-Chu; Hou, You-Hua Expert Opinion on Drug Metabolism & Toxicology, Vol. 11, Issue 7 https://doi.org/10.1517/17425255.2015.1045486	journal	June 2015
Detection of cave pockets in large molecules: Spaces into which internal probes can enter, but external probes from outside cannot Kawabata, Takeshi Biophysics and Physicobiology, Vol. 16, Issue 0 https://doi.org/10.2142/biophysico.16.0_391	journal	January 2019
Sulfation in Dog Tsoi, C.; Swedmark, S. Current Drug Metabolism, Vol. 6, Issue 3 https://doi.org/10.2174/1389200054021816	journal	June 2005
Sulfotransferase Inhibition: Potential Impact of Diet and Environmental Chemicals on Steroid Metabolism and Drug Detoxification Harris, R.; Waring, R. Current Drug Metabolism, Vol. 9, Issue 4 https://doi.org/10.2174/138920008784220637	journal	May 2008
Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus Mulvihill, Eoin D.; Moloney, Nicola M.; Owens, Rebecca A. Frontiers in Microbiology, Vol. 8 https://doi.org/10.3389/fmicb.2017.00418	journal	March 2017
The multi-protein family of sulfotransferases in plants: composition, occurrence, substrate specificity, and functions Hirschmann, Felix; Krause, Florian; Papenbrock, Jutta Frontiers in Plant Science, Vol. 5 https://doi.org/10.3389/fpls.2014.00556	journal	October 2014
Detoxification Strategies for Zearalenone Using Microorganisms: A Review Wang, Nan; Wu, Weiwei; Pan, Jiawen Microorganisms, Vol. 7, Issue 7 https://doi.org/10.3390/microorganisms7070208	journal	July 2019
Involvement of UDP-Glucuronosyltransferases and Sulfotransferases in the Excretion and Tissue Distribution of Resveratrol in Mice Böhmdorfer, Michaela; Szakmary, Akos; Schiestl, Robert Nutrients, Vol. 9, Issue 12 https://doi.org/10.3390/nu9121347	journal	December 2017
Biosynthesis and Characterization of Zearalenone-14-Sulfate, Zearalenone-14-Glucoside and Zearalenone-16-Glucoside Using Common Fungal Strains Borzekowski, Antje; Drewitz, Tatjana; Keller, Julia Toxins, Vol. 10, Issue 3 https://doi.org/10.3390/toxins10030104	journal	March 2018
Total Biosynthesis of Fungal Indole Diterpenes Using Cell Factories Oikawa, Hideaki; Minami, Atsushi; Liu, Chengwei HETEROCYCLES, Vol. 92, Issue 3 https://doi.org/10.3987/REV-15-830	journal	January 2016

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

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