Activation of a Cryptic Manumycin-Type Biosynthetic Gene Cluster of Saccharothrix espanaensis DSM44229 by Series of Genetic Manipulations

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F21%3A43902540" target="_blank" >RIV/60076658:12310/21:43902540 - isvavai.cz</a>

Alternative codes found

RIV/60076658:12520/21:43902540 RIV/60077344:_____/21:00542621 RIV/61388971:_____/21:00542621 RIV/00216208:11110/21:10427916

Result on the web

<a href="https://doi.org/10.3390/microorganisms9030559" target="_blank" >https://doi.org/10.3390/microorganisms9030559</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/microorganisms9030559" target="_blank" >10.3390/microorganisms9030559</a>

Result language

angličtina

Original language name

Activation of a Cryptic Manumycin-Type Biosynthetic Gene Cluster of Saccharothrix espanaensis DSM44229 by Series of Genetic Manipulations

Original language description

(1) Background: Manumycins are small actinomycete polyketides with prominent cancerostatic and immunosuppressive activities via inhibition of various eukaryotic enzymes. Their overall activity towards human cells depends on the structural variability of both their polyketide chains, mainly the upper one. In our genetic screening project to find novel producers of anti-inflammatory manumycins, the strain Saccharothrix espanaensis DSM44229 was identified as containing a novel manumycin-type biosynthetic gene cluster (BGC). (2) Methods: The biosynthetic genes appeared to be silent under all assayed laboratory conditions. Several techniques were used to activate the BGC, including: (i) heterologous expression in various hosts, (ii) overexpression of putative pathway-specific regulatory genes, and (iii) overexpression of a bottleneck cyclizing aminolevulinate synthase gene in both natural and heterologous producers. (3) Results: Multiple novel manumycin-type compounds were produced at various levels by genetically-modified strains, sharing a tetraene lower chain structure with a colabomycin subgroup of manumycins, but possessing much shorter and saturated upper chains. (4) Conclusions: A cryptic manumycin-type BGC was successfully activated by genetic means to gain production of novel manumycin-type compounds for future comparative activity assays. Heterologously produced compounds were identical to those found after final activation of the BGC in the original strain, proving the intactness of the cloned BGC.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10606 - Microbiology

Project

<a href="/en/project/NV17-30091A" target="_blank" >NV17-30091A: Unique biosynthetic enzymes as the key to novel bioactive compounds</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Microorganisms

ISSN

2076-2607

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

3

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

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UT code for WoS article

000633902200001

EID of the result in the Scopus database

2-s2.0-85102123177