New Aminocoumarins from the Rare Actinomycete Catenulispora acidiphila DSM 44928: Identification, Structure Elucidation, and Heterologous Production. Issue 4 (19th February 2014)

• Record Type: Journal Article
• Authors: Zettler, Judith; Xia, Haiyang; Burkard, Nadja; Kulik, Andreas; Grond, Stephanie; Heide, Lutz; Apel, Alexander K.
• Is Part Of: Chembiochem. Volume 15:Issue 4(2014)
• Page Start: 612
• Page End: 621
• Publication Date: 2014-02-19
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300712
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Genome mining led to the discovery of a novel aminocoumarin gene cluster in the rare actinomycete <italic>Catenulispora acidiphila</italic> DSM 44928. Sequence analysis revealed the presence of genes putatively involved in export/resistance, regulation, and biosynthesis of the aminocoumarin moiety and its halogenation, as well as several genes with so far unknown function. Two new aminocoumarins, cacibiocin A and B, were identified in the culture broth of <italic>C. acidiphila</italic>. Heterologous expression of the putative gene cluster in <italic>Streptomyces coelicolor</italic> M1152 confirmed that this cluster is responsible for cacibiocin biosynthesis. Furthermore, total production levels of cacibiocins could be increased by heterologous expression and screening of different culture media from an initial yield of 4.9 mg <sc>L</sc>⁻¹ in <italic>C. acidiphila</italic> to 60 mg <sc>L</sc>⁻¹ in <italic>S. coelicolor</italic> M1152. By HR‐MS and NMR analysis, cacibiocin A was found to contain a 3‐amino‐4, 7‐dihydroxycoumarin moiety linked by an amide bond to a pyrrole‐2, 5‐dicarboxylic acid. The latter structural motif has not been identified previously in any natural compound. Additionally, cacibiocin B contains two chlorine atoms at positions 6′ and 8′ of the aminocoumarin moiety.</p> </abstract>