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

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

  • J Nat Prod. 2024 Sep 27;87(9):2204-2215. doi: 10.1021/acs.jnatprod.4c00516.
Marcelo R de Amorim 1,  Sydney M Schoellhorn 2,  Camila de S Barbosa 3,  Giovana R Mendes 3,  Kamila de L Macedo 1,  Antonio G Ferreira 4,  Tiago Venâncio 4,  Rafael V C Guido 3,  Andrea N L Batista 5,  João M Batista Jr 6,  Elizabeth Skellam 2,  Roberto G S Berlinck 1
Affiliations

Affiliations

  • 1 Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970, São Carlos, SP, Brazil.
  • 2 Department of Chemistry and BioDiscovery Institute, University of North Texas, 1155 Union Circle, Denton, Texas 76203, United States.
  • 3 Instituto de Física de São Carlos, Universidade de São Paulo, CEP 13563-120, São Carlos, SP Brazil.
  • 4 Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905, São Carlos, SP, Brazil.
  • 5 Universidade Federal Fluminense, Instituto de Química, Outeiro de São João Batista s/n, Niterói, RJ, 24020-141, Brazil.
  • 6 Universidade Federal de São Paulo. Instituto de Ciência e Tecnologia, R. Talim 330, São José dos Campos, SP 12231-280, Brazil.
PMID: 39150723 DOI: 10.1021/acs.jnatprod.4c00516
Abstract

Novel open-chain merocytochalasans, perochalasins A-C (1-3), containing an unusual N-O six-membered heterocyclic moiety, were isolated from cultures of the marine-derived Peroneutypa sp. M16 fungus, along with cytochalasin Z27 (4), cytochalasin Z28 (5), [12]-cytochalasin (6), and phenochalasin B (7). The structures of compounds 1-3 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 (7) into 1-3, based on isotope-labeled hydroxylamine (15NH2OH 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 Z27 (4) 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).

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