TY  - JOUR
A1  - Dehm, Daniel
A1  - Krumbholz, Julia
A1  - Baunach, Martin
A1  - Wiebach, Vincent
A1  - Hinrichs, Katrin
A1  - Guljamow, Arthur
A1  - Tabuchi, Takeshi
A1  - Jenke-Kodama, Holger
A1  - Süssmuth, Roderich D.
A1  - Dittmann-Thünemann, Elke
T1  - Unlocking the spatial control of secondary metabolism uncovers hidden natural product diversity in nostoc punctiforme
JF  - ACS chemical biology
N2  - Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis of secondary metabolite gene expression in the model strain Nostoc punctiforme PCC73102 using RNA-seq and fluorescence reporter analysis. Our data demonstrate that the majority of the cryptic gene clusters are not silent but are expressed with regular or sporadic pattern. Cultivation of N. punctiforme using high-density fermentation overrules the spatial control and leads to a pronounced upregulation of more than 50% of biosynthetic gene clusters. Our data suggest that a combination of autocrine factors, a high CO2 level, and high light account for the upregulation of individual pathways. Our overarching study not only sheds light on the strategies of filamentous cyanobacteria to share the enormous metabolic burden connected with the production of specialized molecules but provides an avenue for the genome-based discovery of natural products in multicellular cyanobacteria as exemplified by the discovery of highly unusual variants of the tricyclic peptide microviridin.
Y1  - 2019
U6  - https://doi.org/10.1021/acschembio.9b00240
SN  - 1554-8929
SN  - 1554-8937
VL  - 14
IS  - 6
SP  - 1271
EP  - 1279
PB  - American Chemical Society
CY  - Washington
ER  -