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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The Methionine 549 and Leucine 552 Residues of Friedelin Synthase from Maytenus ilicifolia Are Important for Substrate Binding Specificity

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Author(s):
Mazzeu, Bruna F. [1] ; Souza-Moreira, Tatiana M. [1] ; Oliveira, Andrew A. [2] ; Remlinger, Melissa [1] ; Felippe, Lidiane G. [1] ; Valentini, Sandro R. [3] ; Guido, Rafael V. C. [2] ; Zanelli, Cleslei F. [3] ; Furlan, Maysa [1]
Total Authors: 9
Affiliation:
[1] Univ Estadual Paulista Unesp, Inst Quim, CP 355, BR-14800900 Araraquara, SP - Brazil
[2] Univ Sao Paulo, Inst Fis Sao Carlos, Ctr Pesquisa & Inovacao Biodivers & Farmacos, BR-13563120 Sao Carlos, SP - Brazil
[3] Univ Estadual Paulista UNESP, Fac Ciencias Farmaceut, Rod Araraquara Jau Km 1, BR-14800903 Araraquara, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Molecules; v. 26, n. 22 NOV 2021.
Web of Science Citations: 0
Abstract

Friedelin, a pentacyclic triterpene found in the leaves of the Celastraceae species, demonstrates numerous biological activities and is a precursor of quinonemethide triterpenes, which are promising antitumoral agents. Friedelin is biosynthesized from the cyclization of 2,3-oxidosqualene, involving a series of rearrangements to form a ketone by deprotonation of the hydroxylated intermediate, without the aid of an oxidoreductase enzyme. Mutagenesis studies among oxidosqualene cyclases (OSCs) have demonstrated the influence of amino acid residues on rearrangements during substrate cyclization: loss of catalytic activity, stabilization, rearrangement control or specificity changing. In the present study, friedelin synthase from Maytenus ilicifolia (Celastraceae) was expressed heterologously in Saccharomyces cerevisiae. Site-directed mutagenesis studies were performed by replacing phenylalanine with tryptophan at position 473 (Phe473Trp), methionine with serine at position 549 (Met549Ser) and leucine with phenylalanine at position 552 (Leu552Phe). Mutation Phe473Trp led to a total loss of function; mutants Met549Ser and Leu552Phe interfered with the enzyme specificity leading to enhanced friedelin production, in addition to alpha-amyrin and beta-amyrin. Hence, these data showed that methionine 549 and leucine 552 are important residues for the function of this synthase. (AU)

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
FAPESP's process: 11/10379-1 - CLONING AND CHARACTERIZATION OF OXIDOSQUALENE CYCLASES FROM Maytenus ilicifolia Mart. ex Reissek
Grantee:Tatiana Maria de Souza Moreira
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/25705-0 - Metabolic engineering of the ergosterol pathway of Saccharomyces cerevisiae to improve production of the triterpene friedelin
Grantee:Tatiana Maria de Souza Moreira
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
Grantee:Vanderlan da Silva Bolzani
Support Opportunities: BIOTA-FAPESP Program - Thematic Grants