A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• , Adolf-Reichwein-Strasse 23, 07745 Jena, Germany Department of Biochemical and Chemical Engineering, Technical Biology, Technical University Dortmund, Emil-Figge-Strasse 66, 44227 Dortmund, Germany 10.3762/bjoc.12.274 Abstract Auriculamide is the first natural product known from the predatory bacterium

• Herpetosiphon aurantiacus. It is composed of three unusual building blocks, including the non-proteinogenic amino acid 3-chloro-L-tyrosine, the α-hydroxy acid L-isoleucic acid, and a methylmalonyl-CoA-derived ethane unit. A candidate genetic locus for auriculamide biosynthesis was identified and encodes four

• acid by the enzyme supports the hypothesis that it participates in the biosynthesis of auriculamide. An artificially truncated version of AulA that lacks the first adenylation domain activated this substrate like the full-length enzyme which shows that the first adenylation domain is dispensable

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• metabolites from the H. aurantiacus type strain 114-95T led to the discovery of auriculamide (22) [127]. This natural product is composed of a 2-hydroxy-3-methylvalerate and a 2-amino-1-(3-chloro-4-hydroxyphenyl)pentan-3-one residue. A retrobiosynthetic analysis allowed the assignment of the gene cluster

• , which is responsible for the production of auriculamide. According to the current biosynthetic model, the scaffold of auriculamide is assembled on an NRPS/PKS enzyme complex. A decarboxylation reaction was proposed to shorten the off-loaded carboxylic acid and to give rise to the unusual end group of

• the natural product [127]. Whether auriculamide possesses antibiotic properties is still open. The low fermentation yield prevented biological testing of the isolated compound. More recently, the terpenome of H. aurantiacus 114-95T received some attention. Researchers found two genes in the chromosome