Flavin-Dependent Monooxygenases NotI and NotI' Mediate Spiro-Oxindole Formation in Biosynthesis of the Notoamides

Overview

Journal Chembiochem

Specialty Biochemistry

Date 2020 Apr 5

PMID 32246875

Citations 7

Authors

Amy E Fraley

Hong T Tran

Samantha P Kelly

Sean A Newmister

Ashootosh Tripathi

Hikaru Kato

Sachiko Tsukamoto

Lei Du

Shengying Li

Robert M Williams

David H Sherman

Affiliations

Soon will be listed here.

Abstract

The fungal indole alkaloids are a unique class of complex molecules that have a characteristic bicyclo[2.2.2]diazaoctane ring and frequently contain a spiro-oxindole moiety. While various strains produce these compounds, an intriguing case involves the formation of individual antipodes by two unique species of fungi in the generation of the potent anticancer agents (+)- and (-)-notoamide A. NotI and NotI' have been characterized as flavin-dependent monooxygenases that catalyze epoxidation and semi-pinacol rearrangement to form the spiro-oxindole center within these molecules. This work elucidates a key step in the biosynthesis of the notoamides and provides an evolutionary hypothesis regarding a common ancestor for production of enantiopure notoamides.

Citing Articles

Enzymkatalysierte späte Modifizierungen: Besser spät als nie.

Romero E, Jones B, Hogg B, Rue Casamajo A, Hayes M, Flitsch S Angew Chem Weinheim Bergstr Ger. 2024; 133(31):16962-16993.

PMID: 38505660 PMC: 10946893. DOI: 10.1002/ange.202014931.

Biocatalytic Stereoselective Oxidation of 2-Arylindoles.

Champagne S, Chiang C, Gemmel P, Brooks 3rd C, Narayan A J Am Chem Soc. 2024; 146(4):2728-2735.

PMID: 38237569 PMC: 11214688. DOI: 10.1021/jacs.3c12393.

An NmrA-like enzyme-catalysed redox-mediated Diels-Alder cycloaddition with anti-selectivity.

Liu Z, Rivera S, Newmister S, Sanders J, Nie Q, Liu S Nat Chem. 2023; 15(4):526-534.

PMID: 36635598 PMC: 10073347. DOI: 10.1038/s41557-022-01117-6.

Data Science-Driven Analysis of Substrate-Permissive Diketopiperazine Reverse Prenyltransferase NotF: Applications in Protein Engineering and Cascade Biocatalytic Synthesis of (-)-Eurotiumin A.

Kelly S, Shende V, Flynn A, Dan Q, Ye Y, Smith J J Am Chem Soc. 2022; 144(42):19326-19336.

PMID: 36223664 PMC: 9831672. DOI: 10.1021/jacs.2c06631.

Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins.

Liu Z, Zhao F, Zhao B, Yang J, Ferrara J, Sankaran B Nat Commun. 2021; 12(1):4158.

PMID: 34230497 PMC: 8260726. DOI: 10.1038/s41467-021-24421-0.

References

Kelley L, Mezulis S, Yates C, Wass M, Sternberg M . The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015; 10(6):845-58. PMC: 5298202. DOI: 10.1038/nprot.2015.053. View

Ding Y, de Wet J, Cavalcoli J, Li S, Greshock T, Miller K . Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived Aspergillus sp. J Am Chem Soc. 2010; 132(36):12733-40. PMC: 2941195. DOI: 10.1021/ja1049302. View

Mukai K, Pereira de SantAna D, Hirooka Y, Mercado-Marin E, Stephens D, Kou K . Bioinspired chemical synthesis of monomeric and dimeric stephacidin A congeners. Nat Chem. 2017; 10(1):38-44. PMC: 6317722. DOI: 10.1038/nchem.2862. View

Tsukamoto S, Kato H, Samizo M, Nojiri Y, Onuki H, Hirota H . Notoamides F-K, prenylated indole alkaloids isolated from a marine-derived Aspergillus sp. J Nat Prod. 2008; 71(12):2064-7. DOI: 10.1021/np800471y. View

Newmister S, Gober C, Romminger S, Yu F, Tripathi A, Parra L . OxaD: A Versatile Indolic Nitrone Synthase from the Marine-Derived Fungus Penicillium oxalicum F30. J Am Chem Soc. 2016; 138(35):11176-84. PMC: 5014723. DOI: 10.1021/jacs.6b04915. View

Li S . Prenylated indole derivatives from fungi: structure diversity, biological activities, biosynthesis and chemoenzymatic synthesis. Nat Prod Rep. 2009; 27(1):57-78. DOI: 10.1039/b909987p. View

Tsuda M, Kasai Y, Komatsu K, Sone T, Tanaka M, Mikami Y . Citrinadin A, a novel pentacyclic alkaloid from marine-derived fungus Penicillium citrinum. Org Lett. 2004; 6(18):3087-9. DOI: 10.1021/ol048900y. View

Finefield J, Sherman D, Kreitman M, Williams R . Enantiomeric natural products: occurrence and biogenesis. Angew Chem Int Ed Engl. 2012; 51(20):4802-36. PMC: 3498912. DOI: 10.1002/anie.201107204. View

Miller K, Williams R . Synthetic approaches to the bicyclo[2.2.2]diazaoctane ring system common to the paraherquamides, stephacidins and related prenylated indole alkaloids. Chem Soc Rev. 2009; 38(11):3160-74. PMC: 2839869. DOI: 10.1039/b816705m. View

10.

Li S, Anand K, Tran H, Yu F, Finefield J, Sunderhaus J . Comparative analysis of the biosynthetic systems for fungal bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide, paraherquamide and malbrancheamide pathways. Medchemcomm. 2012; 3(8):987-996. PMC: 3511817. DOI: 10.1039/C2MD20029E. View

11.

Blanchflower S, Banks R, Everett J, Manger B, Reading C . New paraherquamide antibiotics with anthelmintic activity. J Antibiot (Tokyo). 1991; 44(5):492-7. DOI: 10.7164/antibiotics.44.492. View

12.

Li S, Tietz D, Rutaganira F, Kells P, Anzai Y, Kato F . Substrate recognition by the multifunctional cytochrome P450 MycG in mycinamicin hydroxylation and epoxidation reactions. J Biol Chem. 2012; 287(45):37880-90. PMC: 3488060. DOI: 10.1074/jbc.M112.410340. View

13.

Tsukamoto S, Kato H, Greshock T, Hirota H, Ohta T, Williams R . Isolation of notoamide E, a key precursor in the biosynthesis of prenylated indole alkaloids in a marine-derived fungus, Aspergillus sp. J Am Chem Soc. 2009; 131(11):3834-5. PMC: 2671082. DOI: 10.1021/ja810029b. View

14.

Greshock T, Grubbs A, Tsukamoto S, Williams R . A concise, biomimetic total synthesis of stephacidin A and notoamide B. Angew Chem Int Ed Engl. 2007; 46(13):2262-5. DOI: 10.1002/anie.200604378. View

15.

Li S, Finefield J, Sunderhaus J, McAfoos T, Williams R, Sherman D . Biochemical characterization of NotB as an FAD-dependent oxidase in the biosynthesis of notoamide indole alkaloids. J Am Chem Soc. 2011; 134(2):788-91. PMC: 3275806. DOI: 10.1021/ja2093212. View

16.

Eppink M, Schreuder H, van Berkel W . Identification of a novel conserved sequence motif in flavoprotein hydroxylases with a putative dual function in FAD/NAD(P)H binding. Protein Sci. 1998; 6(11):2454-8. PMC: 2143585. DOI: 10.1002/pro.5560061119. View

17.

Watts K, Loveridge S, Tenney K, Media J, Valeriote F, Crews P . Utilizing DART mass spectrometry to pinpoint halogenated metabolites from a marine invertebrate-derived fungus. J Org Chem. 2011; 76(15):6201-8. PMC: 3242642. DOI: 10.1021/jo2009593. View

18.

Artman 3rd G, Grubbs A, Williams R . Concise, asymmetric, stereocontrolled total synthesis of stephacidins A, B and notoamide B. J Am Chem Soc. 2007; 129(19):6336-42. PMC: 2526546. DOI: 10.1021/ja070259i. View

19.

Cacho R, Chooi Y, Zhou H, Tang Y . Complexity generation in fungal polyketide biosynthesis: a spirocycle-forming P450 in the concise pathway to the antifungal drug griseofulvin. ACS Chem Biol. 2013; 8(10):2322-30. PMC: 3821396. DOI: 10.1021/cb400541z. View

20.

Finefield J, Frisvad J, Sherman D, Williams R . Fungal origins of the bicyclo[2.2.2]diazaoctane ring system of prenylated indole alkaloids. J Nat Prod. 2012; 75(4):812-33. PMC: 3485739. DOI: 10.1021/np200954v. View