Biosynthesis of AS2077715 and Funiculosin: Pathway Reconstitution and Identification of Enzymes That Form the All- Cyclopentanetetraol Moiety

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Mar 15

PMID 36920241

Authors

Yalong Zhang

Eun Bin Go

Bruno Perlatti

Lin Wu

Gerald F Bills

Masao Ohashi

Yi Tang

Affiliations

Soon will be listed here.

Abstract

The complete biosynthetic pathways of the potent antifungals AS2077715 () and funiculosin () are reconstituted and characterized. A five-enzyme cascade, including a multifunctional flavin-dependent monooxygenease and a repurposed methyltransferase, is involved to perform the dearomatization, stereoselective ring contraction, and redox transformations to morph a hydroxyphenyl-containing precursor into the unusual all- cyclopentanetetraol moiety.

References

Ye Y, Minami A, Igarashi Y, Izumikawa M, Umemura M, Nagano N . Unveiling the Biosynthetic Pathway of the Ribosomally Synthesized and Post-translationally Modified Peptide Ustiloxin B in Filamentous Fungi. Angew Chem Int Ed Engl. 2016; 55(28):8072-5. DOI: 10.1002/anie.201602611. View

Wang B, Ren J, Li L, Guo F, Pan G, Ai G . Kinamycin biosynthesis employs a conserved pair of oxidases for B-ring contraction. Chem Commun (Camb). 2015; 51(42):8845-8. DOI: 10.1039/c5cc01986a. View

Chakrabarty S, Romero E, Pyser J, Yazarians J, Narayan A . Chemoenzymatic Total Synthesis of Natural Products. Acc Chem Res. 2021; 54(6):1374-1384. PMC: 8210581. DOI: 10.1021/acs.accounts.0c00810. View

Hui C, Craggs L, Antonchick A . Ring contraction in synthesis of functionalized carbocycles. Chem Soc Rev. 2022; 51(20):8652-8675. DOI: 10.1039/d1cs01080h. View

Pan G, Gao X, Fan K, Liu J, Meng B, Gao J . Structure and Function of a C-C Bond Cleaving Oxygenase in Atypical Angucycline Biosynthesis. ACS Chem Biol. 2017; 12(1):142-152. DOI: 10.1021/acschembio.6b00621. View

Sleeman M, Schofield C . Carboxymethylproline synthase (CarB), an unusual carbon-carbon bond-forming enzyme of the crotonase superfamily involved in carbapenem biosynthesis. J Biol Chem. 2003; 279(8):6730-6. DOI: 10.1074/jbc.M311824200. View

Casiraghi G, Zanardi F, Appendino G, Rassu G . The vinylogous aldol reaction: a valuable, yet understated carbon-carbon bond-forming maneuver. Chem Rev. 2001; 100(6):1929-72. DOI: 10.1021/cr990247i. View

Tang M, Lin H, Li D, Zou Y, Li J, Xu W . Discovery of Unclustered Fungal Indole Diterpene Biosynthetic Pathways through Combinatorial Pathway Reassembly in Engineered Yeast. J Am Chem Soc. 2015; 137(43):13724-7. PMC: 4732561. DOI: 10.1021/jacs.5b06108. View

Roh J, Moon J, Youn J, Seo C, Park Y, Kim S . Establishment of Biosynthetic Pathways To Generate Castasterone as the Biologically Active Brassinosteroid in . J Agric Food Chem. 2020; 68(13):3912-3923. DOI: 10.1021/acs.jafc.9b07963. View

10.

Baker Dockrey S, Lukowski A, Becker M, Narayan A . Biocatalytic site- and enantioselective oxidative dearomatization of phenols. Nat Chem. 2018; 10(2):119-125. PMC: 6503525. DOI: 10.1038/nchem.2879. View

11.

Udwary D, Casillas L, Townsend C . Synthesis of 11-hydroxyl O-methylsterigmatocystin and the role of a cytochrome P-450 in the final step of aflatoxin biosynthesis. J Am Chem Soc. 2002; 124(19):5294-303. DOI: 10.1021/ja012185v. View

12.

Rotsaert F, Ding M, Trumpower B . Differential efficacy of inhibition of mitochondrial and bacterial cytochrome bc1 complexes by center N inhibitors antimycin, ilicicolin H and funiculosin. Biochim Biophys Acta. 2007; 1777(2):211-9. PMC: 2677292. DOI: 10.1016/j.bbabio.2007.10.011. View

13.

Ando K, Matsuura I, Nawata Y, Endo H, Sasaki H, Okytomi T . Funiculosin, a new antibiotic. II. Structure elucidation and antifungal activity. J Antibiot (Tokyo). 1978; 31(6):533-8. DOI: 10.7164/antibiotics.31.533. View

14.

Ohsumi K, Masaki T, Takase S, Watanabe M, Fujie A . AS2077715: a novel antifungal antibiotic produced by Capnodium sp. 339855. J Antibiot (Tokyo). 2014; 67(10):707-11. DOI: 10.1038/ja.2014.69. View

15.

Go E, Kim L, Nelson H, Ohashi M, Tang Y . Biosynthesis of the Fusarium Mycotoxin (-)-Sambutoxin. Org Lett. 2021; 23(20):7819-7823. PMC: 8719357. DOI: 10.1021/acs.orglett.1c02836. View

16.

Sato M, Winter J, Kishimoto S, Noguchi H, Tang Y, Watanabe K . Combinatorial Generation of Chemical Diversity by Redox Enzymes in Chaetoviridin Biosynthesis. Org Lett. 2016; 18(6):1446-9. PMC: 4903021. DOI: 10.1021/acs.orglett.6b00380. View

17.

Kahlert L, Bernardi D, Hauser M, Ioca L, Berlinck R, Skellam E . Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products. Chemistry. 2021; 27(46):11895-11903. PMC: 8453496. DOI: 10.1002/chem.202101447. View

18.

Liu N, Hung Y, Gao S, Hang L, Zou Y, Chooi Y . Identification and Heterologous Production of a Benzoyl-Primed Tricarboxylic Acid Polyketide Intermediate from the Zaragozic Acid A Biosynthetic Pathway. Org Lett. 2017; 19(13):3560-3563. PMC: 5673471. DOI: 10.1021/acs.orglett.7b01534. View

19.

Qiu X, Sang Y, Wu H, Xue X, Yan Z, Wang Y . Cleaving arene rings for acyclic alkenylnitrile synthesis. Nature. 2021; 597(7874):64-69. DOI: 10.1038/s41586-021-03801-y. View

20.

Inuki S, Sato K, Zui N, Yamaguchi R, Matsumaru T, Fujimoto Y . Synthetic Studies on FNC-RED and Its Analogues Containing an All -Cyclopentanetetrol Moiety. J Org Chem. 2019; 84(19):12680-12685. DOI: 10.1021/acs.joc.9b02101. View