|
type |
Journal Article |
authors |
Rebets Y, Nadmid S, Paulus C, Dalem C, Hermann J, Hübner H, Rückert C, Kiemer A, Gmeiner P, Kalinowski J, Müller R, Luzhetskyy A |
title |
Perquinolines A-C: Unprecedented Bacterial Tetrahydroisoquinolines Involving an Intriguing Biosynthesis
|
journal |
Angew Chem Int Ed Engl |
Activity |
pqra |
Family |
pqra |
sel |
selected |
ui |
31310031 |
year |
(2019) |
volume |
58 |
number |
37 |
pages |
12930-12934 |
| |
keywords |
tetrahydroisoquinoline natural products biosynthetic gene cluster heterologous expression streptomyces |
abstract |
Metabolic profiling of Streptomyces sp. IB2014/016-6 led to the identification of three new tetrahydroisoquinoline natural products, perquinolines A-C (1-3). Labelled precursor feeding studies and the cloning of the pqr biosynthetic gene cluster revealed that 1-3 are assembled by the action of several unusual enzymes. The biosynthesis starts with the condensation of succinyl-CoA and L-phenylalanine catalysed by the amino-7-oxononanoate synthase-like enzyme PqrA, representing rare chemistry in natural product assembly. The second condensation and cyclization events are conducted by PqrG resembling an acyl-CoA ligase. Last, ATP-grasp RimK-type ligase PqrI completes the biosynthesis by transferring a γ-aminobutyric acid or β-alanine moiety. The discovered pathway represents a new paradigm for assembly of the tetrahydroisoquinoline cores of natural products. |
last changed |
2019/12/19 14:17 |
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