Oxidative functionalization of a halimane diterpenoid achieved by fungal transformation

Author(s)

Monteiro, Afif Felix ^{[1, 2]} ; Righetto, Gabriela Marinho ^[3] ; Simoes, Laura Vilar ^[2] ; de Almeida, Larissa Costa ^[4] ; Costa-Lotufo, Leticia Veras ^[4] ; Baratella da Cunha Camargo, Ilana Lopes ^[3] ; Castro-Gamboa, Ian ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Quim Sao Carlos, CP 780, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Estadual Paulista, UNESP, Nucleo Bioensaios Biossintese & Ecofisiol Prod Na, Inst Quim, Dept Quim Orgincia, Francisco Degni 55, BR-14800900 Araraquara, SP - Brazil

^[3] Univ Sao Paulo, Sao Carlos Inst Phys, POB 369, BR-13556097 Sao Carlos, SP - Brazil

^[4] Univ Sao Paulo, Inst CiPncias BiomM, Av Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 86, p. 550-556, MAY 2019.
• Web of Science Citations: 1

Abstract

Regio and stereoselective activation of sp(3) C-H bonds remain one of the major advantages of biocatalysis over traditional chemocatalytic methods. Herein, we describe the oxy-functionalization of halimane diterpenoid 1 by whole cells of three filamentous fungi, aiming to obtain derivatives with desirable biological properties. After incubating 1 with Fusarium oxysporum, Myrothecium verrucaria, and Rhinocladiella similis at different concentrations and incubation times, four known (3, 5, 6, and 7) and three new (2, 4, and 8) halimane derivatives were obtained and characterized. F. oxysporum catalyzed the hydroxylation of positions C-2 (2) and C-7 (4), while R. similis simultaneously mediated the 2-oxo-functionalization and the hydration of 13,14-(C-C)double bond belonging to an alpha, beta-unsaturated carbonyl system (8). Compounds 1-7 were non-cytotoxic against HCT-116 and MCF-7 cancer cell lines at tested concentrations. However, substrate 1 displayed moderate reduction ability against biofilm produced by Staphylococcus epidermidis ATCC35984 (84% at 1.6 mM), and this effect was retained to some extent by derivatives 4 and 7. These results emphasize the prominent potential of filamentous fungi associated with the microbiota of medicinal plants as versatile catalysts for singularly useful reactions through their complex enzymatic machinery, as well as the high susceptibility of halimane-diterpenoid substrates. (AU)

• FAPESP's process: 16/24969-9 - Evaluation of compounds in multidrug resistant bacterial pathogens as part of the Center for Innovation in Biodiversity and Drug Discovery (CIBFar)
• Grantee: Gabriela Marinho Righetto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC