Investigation of a 6‐MSA Synthase Gene Cluster in  Aspergillus aculeatus  Reveals 6‐MSA‐derived Aculinic Acid, Aculins A–B and Epi‐Aculin A | Zendy

Petersen Lene M. | Zendy; Holm Dorte K. | Zendy; Gotfredsen Charlotte H. | Zendy; Mortensen Uffe H. | Zendy; Larsen Thomas O. | Zendy

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Investigation of a 6‐MSA Synthase Gene Cluster in Aspergillus aculeatus Reveals 6‐MSA‐derived Aculinic Acid, Aculins A–B and Epi‐Aculin A

Author(s) -

Petersen Lene M.,

Holm Dorte K.,

Gotfredsen Charlotte H.,

Mortensen Uffe H.,

Larsen Thomas O.

Publication year - 2015

Publication title -

chembiochem

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.05

H-Index - 126

eISSN - 1439-7633

pISSN - 1439-4227

DOI - 10.1002/cbic.201500210

Subject(s) - aspergillus nidulans , biology , atp synthase , heterologous expression , aspergillus , enzyme , biochemistry , filamentous fungus , heterologous , gene , gene cluster , biosynthesis , genetics , mutant , recombinant dna

Aspergillus aculeatus , a filamentous fungus belonging to the Aspergillus clade Nigri, is an industrial workhorse in enzyme production. Recently we reported a number of secondary metabolites from this fungus; however, its genetic potential for the production of secondary metabolites is vast. In this study we identified a 6‐methylsalicylic acid (6‐MSA) synthase from A. aculeatus , and verified its functionality by episomal expression in A. aculeatus and heterologous expression in A. nidulans . Feeding studies with fully 13 C‐labeled 6‐MSA revealed that 6‐MSA is incorporated into aculinic acid, which further incorporates into three compounds that we name aculins A and B, and epi‐aculin A, described here for the first time. Based on NMR data and bioinformatic studies we propose the structures of the compounds as well as a biosynthetic pathway leading to formation of aculins from 6‐MSA.

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