Cross-chemistry leads to product diversity from atromentin synthetases in Aspergilli from section Nigri

Geib, Elena; Baldeweg, Florian; Doerfer, Maximilian; Nett, Markus; Brock, Matthias

Abstract

Nonribosomal peptide synthetase (NRPS)-like enzymes catalyse the non-oxidative homodimerisation of aromatic α-keto acids, but the exact reaction mechanism is unknown. The furanone-forming thioesterase domain of the Aspergillus terreus aspulvinone E synthetase MelA displays a predicted quinone-forming motif, whereby its catalytic triad contains an essential cysteine indicating an unusual thioester intermediate. To convert MelA into a quinone-forming atromentin synthetase its thioesterase domain was replaced with that from a Paxillus involutus or A. terreus atromentin synthetase. Phylogenetic proximity of donor and acceptor seems important as only replacement with the A. terreus thioesterase was functional. Heterologous expression of atromentin synthetases in Aspergillus niger and Aspergillus oryzae revealed host-dependent product formation whereby cross-chemistry directed atromentin biosynthesis in A. niger towards atrofuranic acid. Screening of aspergilli from section Nigri identified an atromentin synthetase in Aspergillus brasiliensis that produced atrofuranic acid in the homologous host. Therefore, cross-chemistry on quinone cores appears common to section Nigri.

Citation

Geib, E., Baldeweg, F., Doerfer, M., Nett, M., & Brock, M. (2019). Cross-chemistry leads to product diversity from atromentin synthetases in Aspergilli from section Nigri. Cell Chemical Biology, 26(2), 223-234.e6. https://doi.org/10.1016/j.chembiol.2018.10.021

• Journal Article Type: Article
• Acceptance Date: Oct 1, 2018
• Online Publication Date: Dec 6, 2018
• Publication Date: Feb 21, 2019
• Deposit Date: Nov 20, 2018
• Publicly Available Date: Dec 6, 2018
• Journal: Cell Chemical Biology
• Electronic ISSN: 2451-9456
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 2
• Pages: 223-234.e6
• DOI: https://doi.org/10.1016/j.chembiol.2018.10.021
• Keywords: atromentin; aspulvinone E; Aspergillus oryzae; NRPS-like; thioesterase
• Public URL: https://nottingham-repository.worktribe.com/output/1288055
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2451945618303817?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Cross-Chemistry Leads to Product Diversity from Atromentin Synthetases in Aspergilli from Section Nigri; Journal Title: Cell Chemical Biology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.chembiol.2018.10.021; Content Type: article; Copyright: © 2018 Elsevier Ltd.
• Contract Date: Nov 20, 2018