Perquinolines A–C: Unprecedented Bacterial Tetrahydroisoquinolines Involving an Intriguing Biosynthesis

Rebets Y, Nadmid S, Paulus C, Dahlem C, Herrmann J, Hübner H, Rückert C, Kiemer AK, Gmeiner P, Kalinowski J, Müller R, Luzhetskyy A (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Angewandte Chemie International Edition Wiley

DOI: 10.1002/anie.201905538

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 catalyzed 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, an enzyme 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 route for assembling the tetrahydroisoquinoline cores of natural products.

Authors with CRIS profile

Harald Hübner Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie

Additional Organisation(s)

Emil-Fischer-Zentrum (Emil Fischer Center)

Involved external institutions

Helmholtz-Institut für Pharmazeutische Forschung Saarland (HIPS) DE Germany (DE) Universität des Saarlandes (UdS) DE Germany (DE) Universität Bielefeld DE Germany (DE)

How to cite

APA:

Rebets, Y., Nadmid, S., Paulus, C., Dahlem, C., Herrmann, J., Hübner, H.,... Luzhetskyy, A. (2019). Perquinolines A–C: Unprecedented Bacterial Tetrahydroisoquinolines Involving an Intriguing Biosynthesis. Angewandte Chemie International Edition. https://doi.org/10.1002/anie.201905538

MLA:

Rebets, Yuriy, et al. "Perquinolines A–C: Unprecedented Bacterial Tetrahydroisoquinolines Involving an Intriguing Biosynthesis." Angewandte Chemie International Edition (2019).

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