A one-pot chemoenzymatic synthesis for the universal precursor of antidiabetes and antiviral bis-indolylquinones.
Bis-indolylquinones represent a class of fungal natural products that display antiretroviral, antidiabetes, or cytotoxic bioactivities. Recent advances in Aspergillus genomic mining efforts have led to the discovery of the tdiA-E-gene cluster, which is the first genetic locus dedicated to bis-indolylquinone biosynthesis. We have now genetically and biochemically characterized the enzymes TdiA (bis-indolylquinone synthetase) and TdiD (L-tryptophan:phenylpyruvate aminotransferase), which, together, confer biosynthetic abilities for didemethylasterriquinone D to Aspergillus nidulans. This compound is the universal intermediate for all bis-indolylquinones. In this biochemical study of a bis-indolylquinone synthetase and a fungal natural product transaminase, we present a one-pot chemoenzymatic protocol to generate didemethylasterriquinone D in vitro. As TdiA resembles a nonribosomal peptide synthetase, yet catalyzes carbon-carbon-bond formation, we discuss the implications for peptide synthetase chemistry.
Schneider
Patrick
P
Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-Universität, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany.
Weber
Monika
M
Rosenberger
Karen
K
Hoffmeister
Dirk
D
D000998:Antiviral Agents / Q000737:chemistry; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D007004:Hypoglycemic Agents / Q000737:chemistry; D045563:Indolequinones / Q000096:biosynthesis* / Q000737:chemistry; D015394:Molecular Structure; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D051279:Tryptophan Transaminase / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D007004:Hypoglycemic Agents; D045563:Indolequinones; D051279:Tryptophan Transaminase; D010453:Peptide Synthases