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| Status |
Public on Jul 01, 2016 |
| Title |
Generation of new compounds through unbalanced transcription of landomycin A cluster |
| Organism |
Streptomyces albus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
On the example of the biosynthetically exhausted landomycin A cluster we demonstrate unbalancing of gene transcription as an efficient method for the generation of new compounds.
Decoupled from the native regulators LanI and LanK, all landomycin A structural genes were set under the control of a single synthetic promoter and expressed in a heterologous host Streptomyces albus J1074.
Previously being both temporarily and quantitatively regulated, these genes were transcribed as a single polycistronic mRNA leading to the production of four novel and two known compounds.
No glycosylated landomycins were detected though the entire biosynthetic cluster was transcribed, showing the crucial role of the balanced gene expression for the production of landomycin A.
Two new compounds, fridamycin F and G, isolated in this study were shown to originate from the interplay between the expressed biosynthetic pathway and metabolic network of the heterologous host.
Structure activity studies of the isolated compounds as well as results of transcriptome sequencing are discussed in this article.
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| Overall design |
Comparison of gene expression of the H2-26 cosmid (encoding landomycin A biosynthetic genes) with H2-26-act, where an additional constitutive promoter cassette was integrated to drive biosynthetic genes transcription.
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| Contributor(s) |
Myronovskyi M, Brötz E, Rosenkränzer B, Manderscheid N, Tokovenko B, Rebets Y, Luzhetskyy A |
| Citation(s) |
27412461 |
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| Submission date |
Jun 08, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Bogdan Tokovenko |
| Organization name |
Helmholtz Institute for Pharmaceutical Research Saarland
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| Street address |
Campus C2.3
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| City |
Saarbrücken |
| ZIP/Postal code |
66123 |
| Country |
Germany |
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| Platforms (1) |
| GPL21996 |
Illumina HiSeq 2000 (Streptomyces albus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA325059 |
| SRA |
SRP076313 |
