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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.