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doi:10.22028/D291-43671
Titel: | Genome mining for macrolactam-encoding gene clusters allowed for the network-guided isolation of β-amino acid-containing cyclic derivatives and heterologous production of ciromicin A |
VerfasserIn: | Seibel, Elena Um, Soohyun Dayras, Marie Bodawatta, Kasun H. de Kruijff, Martinus Jønsson, Knud A. Poulsen, Michael Kim, Ki Hyun Beemelmanns, Christine |
Sprache: | Englisch |
Titel: | Communications chemistry |
Bandnummer: | 6 |
Heft: | 1 |
Verlag/Plattform: | Springer Nature |
Erscheinungsjahr: | 2023 |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | β-Amino acid-containing macrolactams represent a structurally diverse group of bioactive natural products derived from polyketides; however we are currently lacking a comprehensive overview about their abundance across bacterial families and the underlying biosynthetic diversity. In this study, we employed a targeted β-amino acid-specific homology-based multi-query search to identify potential bacterial macrolactam producers. Here we demonstrate that approximately 10% of each of the identified actinobacterial genera harbor a biosynthetic gene cluster (BGC) encoding macrolactam production. Based on our comparative study, we propose that mutations occurring in specific regions of polyketide synthases (PKS) are the primary drivers behind the variation in macrolactam ring sizes. We successfully validated two producers of ciromicin A from the genus Amycolatopsis, revised the composition of the biosynthetic gene cluster region mte of macrotermycins, and confirmed the ciromicin biosynthetic pathway through heterologous expression. Additionally, network-based metabolomic analysis uncovered three previously unreported macrotermycin congeners from Amycolatopsis sp. M39. The combination of targeted mining and network-based analysis serves as a powerful tool for identifying macrolactam producers and our studies will catalyze the future discovery of yet unreported macrolactams. |
DOI der Erstveröffentlichung: | 10.1038/s42004-023-01034-w |
URL der Erstveröffentlichung: | https://www.nature.com/articles/s42004-023-01034-w |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-436713 hdl:20.500.11880/39134 http://dx.doi.org/10.22028/D291-43671 |
ISSN: | 2399-3669 |
Datum des Eintrags: | 6-Dez-2024 |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Pharmazie |
Professur: | NT - Keiner Professur zugeordnet |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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s42004-023-01034-w.pdf | 2,03 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons