Pleiotropically activation of azaphilone biosynthesis by overexpressing a pathway-specific transcription factor in marine-derived Aspergillus terreus RA2905.

Autor: Zheng YY; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China., Mao JQ; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China., Liu Y; Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany; Department of Bioresources of the Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), 35392 Giessen, Germany., Han N; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China., Lv L; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China., Zhang YH; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China., Chen M; Marine Science & Technology Institute, College of Environmental Science & Engineering, Yangzhou University, 196#, Huayang West Street, Yangzhou 225127, China., Liu ZQ; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China., Shao CL; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China., Yao GS; Fujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Institute of Oceanography, Minjiang University, Fuzhou 350108, China. Electronic address: ygshan@126.com., Wang CY; Key Laboratory of Marine Drugs, the Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China. Electronic address: changyun@ouc.edu.cn.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Dec; Vol. 153, pp. 107832. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1016/j.bioorg.2024.107832
Abstrakt: The genome sequencing of Aspergillus terreus reveals that the vast number of predicted biosynthetic gene clusters have not reflected by the metabolic profile observed under conventional culture conditions. In this study, a silent azaphilone biosynthetic gene cluster was activated by overexpressing a pathway-specific transcription factor gene2642 in marine-derived fungus A. terreus RA2905. Consequently, twenty azaphilone compounds were identified from the OE2642 mutant, including 11 new azaphilones and their precursors, azasperones C-J (1-5, 7-9) and preazasperones A-C (15-17). The structures of those new compounds were unambiguously determined on the basis of NMR and HRESIMS spectra analysis, and the absolute configurations were established depending on ECD calculations. Compounds 1 and 2 were the rarely reported naturally occurring azaphilones with 2-N coupled phenyl-derivative. The bioactivity assay revealed that compounds 18-20 exhibited significant anti-inflammatory activity. Based on the occurrence of diverse intermediates and the putative gene functions, a plausible biosynthetic pathway of these compounds was proposed. The above results demonstrated that overexpression of the pathway-specific transcription factor presents a promising approach for enriching fungal secondary metabolites and accelerating the targeted discovery of novel biosynthetic products.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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