Heterologous expression of 8-demethyl-tetracenomycin (8-dmtc) affected Streptomyces coelicolor life cycle

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  • Gebze Technical University
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Details

Original languageEnglish
Pages (from-to)1107-1118
Number of pages12
JournalBrazilian Journal of Microbiology
Volume52
Issue number3
Early online date20 Apr 2021
Publication statusPublished - Sept 2021
Externally publishedYes

Abstract

Heterologous hosts are highly important to detect the expression of biosynthetic gene clusters that are cryptic or poorly expressed
in their natural hosts. To investigate whether actinorhodin-overproducer Streptomyces coelicolor Δppk mutant strain could be a
possible prototype as a heterologous expression host, a cosmid containing most of the elm gene cluster of Streptomyces olivaceus
Tü2353 was integrated into chromosomes of both S. coelicolor A3(2) and Δppk strains. Interestingly, it was found that the
production of tetracyclic polyketide 8-demethyl-tetracenomycin (8-DMTC) by recombinant strains caused significant changes in
the morphology of cells. All the pellets and clumps were disentangled and mycelia were fragmented in the recombinant strains.
Moreover, they produce neither pigmented antibiotics nor agarase and did not sporulate. By eliminating the elm biosynthesis
genes from the cosmid, we showed that the morphological properties of recombinants were caused by the production of 8-
DMTC. Extracellular application of 8-DMTC on S. coelicolor wild-type cells caused a similar phenotype with the 8-DMTCproducing recombinant strains. The results of this study may contribute to the understanding of the effect of 8-DMTC in
Streptomyces since the morphological changes that we have observed have not been reported before. It is also valuable in that
it provides useful information about the use of Streptomyces as hosts for the heterologous expression of 8-DMTC.

Keywords

    Δppk, Heterologous expression, Streptomyces colony morphology, Pellet disaggregation, 8-DMTC, ∆ppk

ASJC Scopus subject areas

Cite this

Heterologous expression of 8-demethyl-tetracenomycin (8-dmtc) affected Streptomyces coelicolor life cycle. / Cinar, Buse; Demir, Zeynep; Tunca, Sedef.
In: Brazilian Journal of Microbiology, Vol. 52, No. 3, 09.2021, p. 1107-1118.

Research output: Contribution to journalArticleResearchpeer review

Cinar B, Demir Z, Tunca S. Heterologous expression of 8-demethyl-tetracenomycin (8-dmtc) affected Streptomyces coelicolor life cycle. Brazilian Journal of Microbiology. 2021 Sept;52(3):1107-1118. Epub 2021 Apr 20. doi: 10.1007/s42770-021-00499-y
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AU - Cinar, Buse

AU - Demir, Zeynep

AU - Tunca, Sedef

N1 - Funding Information: We are grateful to Dr. Jose A. Salas and Dr. Angel Manteca for their critical reading of the manuscript and valuable comments and suggestions. We would like to thank Dr. Jose A. Salas and Dr. Carmen Mendez (Universidad de Oviedo, Spain) for providing us cos16F4ie.

PY - 2021/9

Y1 - 2021/9

N2 - Heterologous hosts are highly important to detect the expression of biosynthetic gene clusters that are cryptic or poorly expressedin their natural hosts. To investigate whether actinorhodin-overproducer Streptomyces coelicolor Δppk mutant strain could be apossible prototype as a heterologous expression host, a cosmid containing most of the elm gene cluster of Streptomyces olivaceusTü2353 was integrated into chromosomes of both S. coelicolor A3(2) and Δppk strains. Interestingly, it was found that theproduction of tetracyclic polyketide 8-demethyl-tetracenomycin (8-DMTC) by recombinant strains caused significant changes inthe morphology of cells. All the pellets and clumps were disentangled and mycelia were fragmented in the recombinant strains.Moreover, they produce neither pigmented antibiotics nor agarase and did not sporulate. By eliminating the elm biosynthesisgenes from the cosmid, we showed that the morphological properties of recombinants were caused by the production of 8-DMTC. Extracellular application of 8-DMTC on S. coelicolor wild-type cells caused a similar phenotype with the 8-DMTCproducing recombinant strains. The results of this study may contribute to the understanding of the effect of 8-DMTC inStreptomyces since the morphological changes that we have observed have not been reported before. It is also valuable in thatit provides useful information about the use of Streptomyces as hosts for the heterologous expression of 8-DMTC.

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