Biosynthesis of phomactins produced by the fungus Biatriospora sp. CBMAI 1333 and alpha-aminopyrones produced by the fungus Aspergillus sp. DLM38

• Grant number: 22/07831-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): November 30, 2022
• Effective date (End): October 29, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Roberto Gomes de Souza Berlinck
• Grantee: Lamonielli Fagá Michaliski
• Supervisor: Yi Tang
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Research place: University of California, Los Angeles (UCLA), United States
• Associated to the scholarship: 19/07894-3 - Discovery of bioactive secondary metabolites produced by microbial strains from isolated environments and study of the biosynthesis of alpha-aminopyrones produced by Aspergillus sp. DLM38, BP.DD

Abstract

This research proposal aims to advance in the elucidation of fungal biosynthetic pathways using genomics and metabolomics approaches. The first group of compounds to be investigated are the phomactins, diterpenes that inhibit the platelet aggregating factor receptor and reduce the repopulation of tumor cells after radiotherapy. The producer fungus of phomactins, Biatriospora sp. CBMAI 1333, had its genome sequenced and analyzed using bioinformatics. Two putative phomactin biosynthetic gene clusters were found. We also aim to investigate the biosynthesis of the ±-aminopyrone naphthoquinoneimine, a NRPS-PKS-derived compound produced by Aspergillus sp. DLM38 with antiviral activity. Aspergillus sp. DLM38 genome was also sequenced and analyzed by bioinformatics. Two putative ±-aminopyrone biosynthetic gene clusters were assigned as coding the biosynthesis of naphthoquinoneimine. We propose to investigate the biosynthesis of phomactins and ±-aminopyrones using gene knock-out and/or heterologous expression. We also intend to identify biosynthetic intermediates by comparing the chemical profile of the wild-type and knock-out mutant or heterologous host strains using UPLC-QToF-MS/MS analysis. We hope to contribute to the knowledge on the biosynthesis of important groups of natural products with relevant potential therapeutic applications. (AU)