Biosynthesis of acurin A and B in Aspergillus aculeatus

M.L. Nielsen, P.P. Wolff, L.M. Petersen, L.N. Andersen, T.I. Petersen, D.K. Holm, U.H. Mortensen, C.S. Nødvig, T.O. Larsen, J.B. Hoof

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Abstract

Aspergillus aculeatus is known for the commercial utilization in production of several enzymes. We have identified two stereoisomeric compounds of mixed polyketide-nonribosomal peptide origin in the extracts of A. aculeatus that we named acurin A and acurin B. The structures of the compounds strongly resemble the structure of the mycotoxin fusarin C produced by several Fusarium species. CRISPR-Cas9 was used to construct a non-homologous end-joining deficient strain of A. aculeatus, which enabled efficient gene deletions in the acurin gene cluster. Using RT-qPCR in combination with metabolite profiling of gene deletion strains, the acurin producing gene cluster was delineated, which allowed us to propose a biosynthetic pathway for formation of acurin. Our results show that acurin, in contrast to fusarin C, is biosynthesized by an individual polyketide synthase and non-ribosomal synthetase. At least six other enzymatic activities are required for the biosynthesis of acurin. This study shows how we exploit the CRISPR-Cas9 system for the rapid construction of fungal host strains that can be readily engineered to generate valuable knowledge.
Original languageEnglish
Publication date2017
Publication statusPublished - 2017
Event29th Fungal Genetics Conference - Pacific Grove, United States
Duration: 14 Mar 201719 Mar 2017
Conference number: 29
http://www.genetics-gsa.org/fungal/2017/

Conference

Conference29th Fungal Genetics Conference
Number29
Country/TerritoryUnited States
CityPacific Grove
Period14/03/201719/03/2017
Internet address

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  • 29th Fungal Genetics Conference

    Jane Lind Nybo Rasmussen (Speaker)

    14 Mar 201719 Mar 2017

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