Structure and Biosynthesis of Perochalasins A-C, Open-Chain Merocytochalasans Produced by the Marine-Derived Fungus Peroneutypa sp. M16

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de Amorim, Marcelo R. ; Schoellhorn, Sydney M. ; de S. Barbosa, Camila ; Mendes, Giovana R. ; de L. Macedo, Kamila ; Ferreira, Antonio G. ; Venancio, Tiago ; Guido, Rafael V. C. ; Batista, Andrea N. L. ; Batista Jr, Joao M. ; Skellam, Elizabeth ; Berlinck, Roberto G. S.

• Document type: Journal article
• Source: Journal of Natural Products; v. 87, n. 9, p. 12-pg., 2024-08-16.

Abstract

Novel open-chain merocytochalasans, perochalasins A-C (<bold>1</bold>-<bold>3</bold>), containing an unusual N-O six-membered heterocyclic moiety, were isolated from cultures of the marine-derived Peroneutypa sp. M16 fungus, along with cytochalasin Z(27) (<bold>4</bold>), cytochalasin Z(28) (<bold>5</bold>), [12]-cytochalasin (<bold>6</bold>), and phenochalasin B (<bold>7</bold>). The structures of compounds <bold>1</bold>-<bold>3</bold> were established by analysis of the spectroscopic data. Full genome sequencing of Peroneutypa sp. M16 enabled the identification of a cytochalasan biosynthetic gene cluster and a proposal for the biosynthetic assembly of perochalasins. The proposal is supported by the nonenzymatic conversion of phenochalasin B (<bold>7</bold>) into <bold>1</bold>-<bold>3</bold>, based on isotope-labeled hydroxylamine ((NH2OH)-N-15 and ND2OD) feeding studies in vivo and in vitro. In contrast to other merocytochalasans, these are the first cytochalasans confirmed to arise via nucleophilic addition and at a distinct location from the reactive macrocycle olefin, potentially expanding further the range of merocytochalasans to be discovered or engineered. Cytochalasin Z(27) (<bold>4</bold>) exhibited antiplasmodial activities in the low micromolar range against the chloroquine-sensitive Plasmodium falciparum 3D7 strain as well as against resistant strains of the parasite (Dd2, TM90C6B, and 3D7r_MMV848). (AU)

• FAPESP's process: 20/01229-5 - Bioactive metabolites of bacterial flora microorganisms from non-filtering marine animals
• Grantee: Marcelo Rodrigues de Amorim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/01017-0 - Multi-use instrument approved and awarded in the project 2013/50228-8, name of instrument: ultra-performance liquid chromatograph coupled with a high resolution mass spectrometer
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 19/22319-5 - Vibrational circular dichroism spectral markers: facilitating absolute configuration assignment of natural products
• Grantee: João Marcos Batista Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/17721-9 - The role of Chemistry in holobiont adaptation
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/12904-5 - Discovery of Plasmodium falciparum inhibitors from Cerrado plants as lead compounds candidates for malaria: integrated studies of ultra-efficient chromatography, spectroscopy, and biological assays
• Grantee: Rafael Victorio Carvalho Guido
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• FAPESP's process: 23/12475-5 - Systematizing chiroptical properties of lignans: implications for correct absolute configuration assignments
• Grantee: João Marcos Batista Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/15570-6 - Investigating the biosynthesis of cytochalasans from the marine-derived fungus Peroneutypa sp. M16
• Grantee: Marcelo Rodrigues de Amorim
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor