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Angew Chem Int Ed Engl. 2019 Sep 9;58(37):12930-12934. doi: 10.1002/anie.201905538. Epub 2019 Aug 21.

Perquinolines A-C: Unprecedented Bacterial Tetrahydroisoquinolines Involving an Intriguing Biosynthesis.

Author information

1
Department of Pharmacy, Pharmaceutical Biotechnology, University of Saarland, Campus, Bld. C2 3, Saarbrucken, 66123, Germany.
2
Department of Pharmacy, Pharmaceutical Biology, University of Saarland, Campus, Bld. C2 3, Saarbrucken, 66123, Germany.
3
Department Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus, Bld. 8 1, Saarbrucken, 66123, Germany.
4
Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger-Strasse 10, 91058, Erlangen, Germany.
5
Center for Biotechnology-CeBiTec, University of Bielefeld, Universitätsstraße 25, 33615, Bielefeld, Germany.

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.

KEYWORDS:

8-amino-7-oxononanoate synthase; Streptomyces; biosynthesis; natural product; tetrahydroisoquinoline

PMID:
31310031
DOI:
10.1002/anie.201905538

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