Publication

Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi

Zwahlen, R., Pohl, C., Bovenberg, R. A. L. & Driessen, A. J. M., Sep-2019, In : ACS Synthetic Biology. 8, 8, p. 1776-1787 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Zwahlen, R., Pohl, C., Bovenberg, R. A. L., & Driessen, A. J. M. (2019). Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi. ACS Synthetic Biology, 8(8), 1776-1787. https://doi.org/10.1021/acssynbio.9b00106

Author

Zwahlen, Reto ; Pohl, Carsten ; Bovenberg, Roel A. L. ; Driessen, Arnold J. M. / Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi. In: ACS Synthetic Biology. 2019 ; Vol. 8, No. 8. pp. 1776-1787.

Harvard

Zwahlen, R, Pohl, C, Bovenberg, RAL & Driessen, AJM 2019, 'Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi', ACS Synthetic Biology, vol. 8, no. 8, pp. 1776-1787. https://doi.org/10.1021/acssynbio.9b00106

Standard

Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi. / Zwahlen, Reto; Pohl, Carsten; Bovenberg, Roel A. L.; Driessen, Arnold J. M.

In: ACS Synthetic Biology, Vol. 8, No. 8, 09.2019, p. 1776-1787.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Zwahlen R, Pohl C, Bovenberg RAL, Driessen AJM. Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi. ACS Synthetic Biology. 2019 Sep;8(8):1776-1787. https://doi.org/10.1021/acssynbio.9b00106


BibTeX

@article{652bd0b86318477d980fbdbebb5137d4,
title = "Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi",
abstract = "Filamentous fungi are known producers of bioactive natural products, low molecular weight molecules that arise from secondary metabolism. MbtH-like proteins (MLPs) are small (~10 kDa) proteins, which associate non-covalently with adenylation domains of some bacterial nonribosomal peptide synthetases (NRPS). MLPs promote the folding, stability, and activity of NRPS enzymes. MLPs are highly conserved amongst a wide range of bacteria, however, they are absent from all fungal species sequenced to date. We analyzed the interaction potential of bacterial MLPs with eukaryotic NRPS enzymes first using crystal structures, with results suggesting a conservation of the interaction surface. Subsequently, we transformed five MLPs into Penicillium chrysogenum strains and analyzed changes in NRPS-derived metabolite profiles. Three of the five transformed MLPs increased the rate of nonribosomal peptide formation and elevated the concentrations of intermediate and final products of the penicillin, roquefortine, chrysogine and fungisporin biosynthetic pathways. Our results suggest that even though MLPs are not found in the fungal domain of life, they can be used in fungal hosts as a tool for natural product discovery and biotechnological production.",
keywords = "MbtH-like protein, nonribosomal peptide synthetases, Penicillium chrysogenum, secondary metabolism, fungal natural products, GENE-CLUSTER, SORBICILLIN BIOSYNTHESIS, PENICILLIUM, DOMAIN, GENOME, IDENTIFICATION, EXPRESSION, SEQUENCE, ENTEROBACTIN, ADENYLATION",
author = "Reto Zwahlen and Carsten Pohl and Bovenberg, {Roel A. L.} and Driessen, {Arnold J. M.}",
year = "2019",
month = "9",
doi = "10.1021/acssynbio.9b00106",
language = "English",
volume = "8",
pages = "1776--1787",
journal = "ACS Synthetic Biology",
issn = "2161-5063",
publisher = "AMER CHEMICAL SOC",
number = "8",

}

RIS

TY - JOUR

T1 - Bacterial MbtH-like proteins stimulate nonribosomal peptide synthetase-derived secondary metabolism in the filamentous fungi

AU - Zwahlen, Reto

AU - Pohl, Carsten

AU - Bovenberg, Roel A. L.

AU - Driessen, Arnold J. M.

PY - 2019/9

Y1 - 2019/9

N2 - Filamentous fungi are known producers of bioactive natural products, low molecular weight molecules that arise from secondary metabolism. MbtH-like proteins (MLPs) are small (~10 kDa) proteins, which associate non-covalently with adenylation domains of some bacterial nonribosomal peptide synthetases (NRPS). MLPs promote the folding, stability, and activity of NRPS enzymes. MLPs are highly conserved amongst a wide range of bacteria, however, they are absent from all fungal species sequenced to date. We analyzed the interaction potential of bacterial MLPs with eukaryotic NRPS enzymes first using crystal structures, with results suggesting a conservation of the interaction surface. Subsequently, we transformed five MLPs into Penicillium chrysogenum strains and analyzed changes in NRPS-derived metabolite profiles. Three of the five transformed MLPs increased the rate of nonribosomal peptide formation and elevated the concentrations of intermediate and final products of the penicillin, roquefortine, chrysogine and fungisporin biosynthetic pathways. Our results suggest that even though MLPs are not found in the fungal domain of life, they can be used in fungal hosts as a tool for natural product discovery and biotechnological production.

AB - Filamentous fungi are known producers of bioactive natural products, low molecular weight molecules that arise from secondary metabolism. MbtH-like proteins (MLPs) are small (~10 kDa) proteins, which associate non-covalently with adenylation domains of some bacterial nonribosomal peptide synthetases (NRPS). MLPs promote the folding, stability, and activity of NRPS enzymes. MLPs are highly conserved amongst a wide range of bacteria, however, they are absent from all fungal species sequenced to date. We analyzed the interaction potential of bacterial MLPs with eukaryotic NRPS enzymes first using crystal structures, with results suggesting a conservation of the interaction surface. Subsequently, we transformed five MLPs into Penicillium chrysogenum strains and analyzed changes in NRPS-derived metabolite profiles. Three of the five transformed MLPs increased the rate of nonribosomal peptide formation and elevated the concentrations of intermediate and final products of the penicillin, roquefortine, chrysogine and fungisporin biosynthetic pathways. Our results suggest that even though MLPs are not found in the fungal domain of life, they can be used in fungal hosts as a tool for natural product discovery and biotechnological production.

KW - MbtH-like protein

KW - nonribosomal peptide synthetases

KW - Penicillium chrysogenum

KW - secondary metabolism

KW - fungal natural products

KW - GENE-CLUSTER

KW - SORBICILLIN BIOSYNTHESIS

KW - PENICILLIUM

KW - DOMAIN

KW - GENOME

KW - IDENTIFICATION

KW - EXPRESSION

KW - SEQUENCE

KW - ENTEROBACTIN

KW - ADENYLATION

U2 - 10.1021/acssynbio.9b00106

DO - 10.1021/acssynbio.9b00106

M3 - Article

VL - 8

SP - 1776

EP - 1787

JO - ACS Synthetic Biology

JF - ACS Synthetic Biology

SN - 2161-5063

IS - 8

ER -

ID: 90448365