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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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. / Seibel, Elena; Um, Soohyun; Dayras, Marie; Bodawatta, Kasun H.; de Kruijff, Martinus; Jønsson, Knud A.; Poulsen, Michael; Kim, Ki Hyun; Beemelmanns, Christine.

In: Communications Chemistry, Vol. 6, 257, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Seibel, E, Um, S, Dayras, M, Bodawatta, KH, de Kruijff, M, Jønsson, KA, Poulsen, M, Kim, KH & Beemelmanns, C 2023, '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', Communications Chemistry, vol. 6, 257. https://doi.org/10.1038/s42004-023-01034-w

APA

Seibel, E., Um, S., Dayras, M., Bodawatta, K. H., de Kruijff, M., Jønsson, K. A., Poulsen, M., Kim, K. H., & Beemelmanns, C. (2023). 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. Communications Chemistry, 6, [257]. https://doi.org/10.1038/s42004-023-01034-w

Vancouver

Seibel E, Um S, Dayras M, Bodawatta KH, de Kruijff M, Jønsson KA et al. 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. Communications Chemistry. 2023;6. 257. https://doi.org/10.1038/s42004-023-01034-w

Author

Seibel, Elena ; Um, Soohyun ; Dayras, Marie ; Bodawatta, Kasun H. ; de Kruijff, Martinus ; Jønsson, Knud A. ; Poulsen, Michael ; Kim, Ki Hyun ; Beemelmanns, Christine. / 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. In: Communications Chemistry. 2023 ; Vol. 6.

Bibtex

@article{58a91d16cd174763bf1f1ba6cf5156da,

title = "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",

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.",

author = "Elena Seibel and Soohyun Um and Marie Dayras and Bodawatta, {Kasun H.} and {de Kruijff}, Martinus and J{\o}nsson, {Knud A.} and Michael Poulsen and Kim, {Ki Hyun} and Christine Beemelmanns",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s42004-023-01034-w",

language = "English",

volume = "6",

journal = "Communications Chemistry",

issn = "2399-3669",

publisher = "Springer",

}

RIS

TY - JOUR

T1 - 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

AU - Seibel, Elena

AU - Um, Soohyun

AU - Dayras, Marie

AU - Bodawatta, Kasun H.

AU - de Kruijff, Martinus

AU - Jønsson, Knud A.

AU - Poulsen, Michael

AU - Kim, Ki Hyun

AU - Beemelmanns, Christine

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s42004-023-01034-w

DO - 10.1038/s42004-023-01034-w

M3 - Journal article

C2 - 37985888

AN - SCOPUS:85177210507

VL - 6

JO - Communications Chemistry

JF - Communications Chemistry

SN - 2399-3669

M1 - 257

ER -

ID: 374451960

Department of Biology