Abstract
Trioxacarcin A is a polyoxygenated, structurally complex antibiotic produced by Streptomyces spp., which possesses high anti-bacterial, anti-malaria, and anti-tumor activities. The trioxacarcin biosynthetic pathway involves type II polyketide synthases (PKSs) with l-isoleucine as a unique starter unit, as well as many complex post-PKS tailoring enzymes and resistance and regulatory proteins. In this work, two regulatory genes, txn9 coding for a Streptomyces antibiotic regulatory protein family regulator and txn11 for a two-component response regulator, were revealed to be absolutely required for trioxacarcin production by individually inactivating all the six annotated regulatory genes in the txn cluster. Complementation assay suggested that these two activators do not have a regulatory cascade relationship. Moreover, transcriptional analysis showed that they activate 15 of the 28 txn operons, indicating that a complicated regulatory network is involved in the trioxacarcin production. Information gained from this study may be useful for improving the production of the highly potent trioxacarcin A.
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Acknowledgments
We thank Dr. Weihong Jiang (Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) for kindly providing us the pSET1521 plasmid. This work was financially supported by grants from the National Natural Science Foundation of P. R. China (81202442).
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Kui Yang and Li-Hua Qi have contributed equally to this work.
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Yang, K., Qi, LH., Zhang, M. et al. The SARP Family Regulator Txn9 and Two-Component Response Regulator Txn11 are Key Activators for Trioxacarcin Biosynthesis in Streptomyces bottropensis . Curr Microbiol 71, 458–464 (2015). https://doi.org/10.1007/s00284-015-0868-9
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DOI: https://doi.org/10.1007/s00284-015-0868-9