Engineering Sulfonate Group Donor Regeneration Systems to Boost Biosynthesis of Sulfated Compounds

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Nov 10

PMID 37949843

Authors

Ruirui Xu

Weijao Zhang

Xintong Xi

Jiamin Chen

Yang Wang

Guocheng Du

Jianghua Li

Jian Chen

Zhen Kang

Affiliations

Soon will be listed here.

Abstract

Sulfonation as one of the most important modification reactions in nature is essential for many biological macromolecules to function. Development of green sulfonate group donor regeneration systems to efficiently sulfonate compounds of interest is always attractive. Here, we design and engineer two different sulfonate group donor regeneration systems to boost the biosynthesis of sulfated compounds. First, we assemble three modules to construct a 3'-phosphoadenosine-5'-phosphosulfate (PAPS) regeneration system and demonstrate its applicability for living cells. After discovering adenosine 5'-phosphosulfate (APS) as another active sulfonate group donor, we engineer a more simplified APS regeneration system that couples specific sulfotransferase. Next, we develop a rapid indicating system for characterizing the activity of APS-mediated sulfotransferase to rapidly screen sulfotransferase variants with increased activity towards APS. Eventually, the active sulfonate group equivalent values of the APS regeneration systems towards trehalose and p-coumaric acid reach 3.26 and 4.03, respectively. The present PAPS and APS regeneration systems are environmentally friendly and applicable for scaling up the biomanufacturing of sulfated products.

Citing Articles

Microbial production of chondroitin sulfate and its derivatives.

Li J, Zhang J, Tan H Sci China Life Sci. 2024; 68(3):871-873.

PMID: 39666218 DOI: 10.1007/s11427-024-2805-1.

Polysaccharide sulfotransferases: the identification of putative sequences and respective functional characterisation.

Mistry R, Byrne D, Starns D, Barsukov I, Yates E, Fernig D Essays Biochem. 2024; 68(4):431-447.

PMID: 38712401 PMC: 11625862. DOI: 10.1042/EBC20230094.

Engineering sulfonate group donor regeneration systems to boost biosynthesis of sulfated compounds.

Xu R, Zhang W, Xi X, Chen J, Wang Y, Du G Nat Commun. 2023; 14(1):7297.

PMID: 37949843 PMC: 10638397. DOI: 10.1038/s41467-023-43195-1.

References

Malojcic G, Owen R, Grimshaw J, Brozzo M, Dreher-Teo H, Glockshuber R . A structural and biochemical basis for PAPS-independent sulfuryl transfer by aryl sulfotransferase from uropathogenic Escherichia coli. Proc Natl Acad Sci U S A. 2008; 105(49):19217-22. PMC: 2614742. DOI: 10.1073/pnas.0806997105. View

Radka C, Miller D, Frank M, Rock C . Biochemical characterization of the first step in sulfonolipid biosynthesis in Alistipes finegoldii. J Biol Chem. 2022; 298(8):102195. PMC: 9304779. DOI: 10.1016/j.jbc.2022.102195. View

Badri A, Williams A, Xia K, Linhardt R, Koffas M . Increased 3'-Phosphoadenosine-5'-phosphosulfate Levels in Engineered Escherichia coli Cell Lysate Facilitate the In Vitro Synthesis of Chondroitin Sulfate A. Biotechnol J. 2019; 14(9):e1800436. DOI: 10.1002/biot.201800436. View

Mauvais-Jarvis F, Clegg D, Hevener A . The role of estrogens in control of energy balance and glucose homeostasis. Endocr Rev. 2013; 34(3):309-38. PMC: 3660717. DOI: 10.1210/er.2012-1055. View

Duffel M, Marshal A, McPhie P, Sharma V, Jakoby W . Enzymatic aspects of the phenol (aryl) sulfotransferases. Drug Metab Rev. 2002; 33(3-4):369-95. DOI: 10.1081/dmr-120001394. View

Parnell A, Mordhorst S, Kemper F, Giurrandino M, Prince J, Schwarzer N . Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures. Proc Natl Acad Sci U S A. 2018; 115(13):3350-3355. PMC: 5879653. DOI: 10.1073/pnas.1710741115. View

Bao F, Yan H, Sun H, Yang P, Liu G, Zhou X . Hydrolysis of by-product adenosine diphosphate from 3'-phosphoadenosine-5'-phosphosulfate preparation using Nudix hydrolase NudJ. Appl Microbiol Biotechnol. 2015; 99(24):10771-8. DOI: 10.1007/s00253-015-6911-8. View

Chen B, Tong X, Zhang X, Gui W, Ai G, Huang L . Sulfation modification of dopamine in brain regulates aggregative behavior of animals. Natl Sci Rev. 2022; 9(4):nwab163. PMC: 9072122. DOI: 10.1093/nsr/nwab163. View

Bhaskar U, Li G, Fu L, Onishi A, Suflita M, Dordick J . Combinatorial one-pot chemoenzymatic synthesis of heparin. Carbohydr Polym. 2015; 122:399-407. PMC: 4379424. DOI: 10.1016/j.carbpol.2014.10.054. View

10.

Jin X, Li Q, Wang Y, Zhang W, Xu R, Li J . Optimizing the sulfation-modification system for scale preparation of chondroitin sulfate A. Carbohydr Polym. 2020; 246:116570. DOI: 10.1016/j.carbpol.2020.116570. View

11.

Motomura K, Hirota R, Okada M, Ikeda T, Ishida T, Kuroda A . A new subfamily of polyphosphate kinase 2 (class III PPK2) catalyzes both nucleoside monophosphate phosphorylation and nucleoside diphosphate phosphorylation. Appl Environ Microbiol. 2014; 80(8):2602-8. PMC: 3993171. DOI: 10.1128/AEM.03971-13. View

12.

Kumar S, Stecher G, Li M, Knyaz C, Tamura K . MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol Biol Evol. 2018; 35(6):1547-1549. PMC: 5967553. DOI: 10.1093/molbev/msy096. View

13.

Mougous J, Petzold C, Senaratne R, Lee D, Akey D, Lin F . Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis. Nat Struct Mol Biol. 2004; 11(8):721-9. DOI: 10.1038/nsmb802. View

14.

Burkart M, Izumi M, Chapman E, Lin C, Wong C . Regeneration of PAPS for the enzymatic synthesis of sulfated oligosaccharides. J Org Chem. 2000; 65(18):5565-74. DOI: 10.1021/jo000266o. View

15.

Xu R, Zhang W, Xi X, Chen J, Wang Y, Du G . Engineering sulfonate group donor regeneration systems to boost biosynthesis of sulfated compounds. Nat Commun. 2023; 14(1):7297. PMC: 10638397. DOI: 10.1038/s41467-023-43195-1. View

16.

Xie L, Xiao D, Wang X, Wang C, Bai J, Yue Q . Combinatorial Biosynthesis of Sulfated Benzenediol Lactones with a Phenolic Sulfotransferase from Fusarium graminearum PH-1. mSphere. 2020; 5(6). PMC: 7690957. DOI: 10.1128/mSphere.00949-20. View

17.

Boom J, Heider D, Martin S, Pastore A, Mueller J . 3'-Phosphoadenosine 5'-phosphosulfate (PAPS) synthases, naturally fragile enzymes specifically stabilized by nucleotide binding. J Biol Chem. 2012; 287(21):17645-17655. PMC: 3366831. DOI: 10.1074/jbc.M111.325498. View

18.

Huang H, Hou X, Xu R, Deng Z, Wang Y, Du G . Structure and cleavage pattern of a hyaluronate 3-glycanohydrolase in the glycoside hydrolase 79 family. Carbohydr Polym. 2021; 277:118838. DOI: 10.1016/j.carbpol.2021.118838. View

19.

Burkart , Izumi , Wong . Enzymatic Regeneration of 3'-Phosphoadenosine-5'-Phosphosulfate Using Aryl Sulfotransferase for the Preparative Enzymatic Synthesis of Sulfated Carbohydrates. Angew Chem Int Ed Engl. 1999; 38(18):2747-2750. DOI: 10.1002/(sici)1521-3773(19990917)38:18<2747::aid-anie2747>3.0.co;2-2. View

20.

Men P, Geng C, Zhang X, Zhang W, Xie L, Feng D . Biosynthesis mechanism, genome mining and artificial construction of echinocandin O-sulfonation. Metab Eng. 2022; 74:160-167. DOI: 10.1016/j.ymben.2022.10.006. View