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Discovery of the streptoketides by direct cloning and rapid heterologous expression of a cryptic PKS II gene cluster from streptomyces sp. Tü 6314.
J. Org. Chem. 85, 664-673 (2020)
Genome sequencing and bioinformatic analysis have identified numerous cryptic gene clusters that have the potential to produce novel natural products. Within this work, we identified a cryptic type II PKS gene cluster (skt) from Streptomyces sp. Tu 6314. Facilitated by linear plus linear homologous recombination-mediated recombineering (LLHR), we directly cloned the skt gene cluster using the Streptomyces site-specific integration vector pSET152. Direct cloning allowed for rapid heterologous expression in Streptomyces coelicolor, leading to the identification and structural characterization of six polyketides (three known compounds and new streptoketides), four of which exhibit anti-HIV activities. Our study shows that the pSET152 vector can be directly used for LLHR, expanding the Rec/ET direct cloning toolbox and providing the possibility for rapid heterologous expression of gene clusters from Streptomyces.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Microbial Natural-products; Starter Unit; Polyketide Synthase; Biosynthesis; Daunorubicin; Dna; Anthracycline; Ketosynthase; Doxorubicin; Coelicolor
ISSN (print) / ISBN
0022-3263
e-ISSN
1520-6904
Zeitschrift
Journal of Organic Chemistry, The
Quellenangaben
Band: 85,
Heft: 2,
Seiten: 664-673
Verlag
American Chemical Society (ACS)
Verlagsort
1155 16th St, Nw, Washington, Dc 20036 Usa
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Virology (VIRO)