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Rational design for heterologous production of aurovertin-type compounds in Aspergillus nidulans

  • Applied genetics and molecular biotechnology
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Abstract

Aurovertins are the structurally diverse polyketides that distribute widely in different fungal species. They feature a 2,6-dioxabicyclo[3.2.1]-octane ring in structure and exhibit the potential antitumor activity against breast cancer as F1-ATPase β subunit inhibitor. In this study, we constructed the biosynthetic pathway of aurovertin in an Aspergillus nidulans host and obtained seven aurovertin-type compounds. Surprisingly, three new aurovertin geometric isomers were characterized. By introducing an inducible promoter xylP(p) in the pathway gene acyltransferase aurG, we can control the product ratios among different aurovertin compounds by adding glucose and/or inducer xylose. The yields of aurovertins could be increased up to about 20 times by adding a constitutive promoter gpdA(p) to transcription factor AurF, which indicates AurF’s positive role in the biosynthesis of aurovertin. Taken together, our results provided not only an efficient way to generate bioactive fungal natural products but also realized the rational controlling their yields with designed promoters.

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Acknowledgements

We thank Dr. Yi Tang (University of California, in Los Angeles) for providing Calcarisporium arbuscular strain. We thank Drs. Jinwei Ren and Wenzhao Wang (Institute of Microbiology, CAS) for NMR and MS data collection. We thank Dr. Aili Fan for the helpful discussion for NMR spectra. W.B.Y. is a scholar of “the 100 Talents Project” of CAS.

Funding

This work is supported by the National Natural Science Foundation of China (31470178) and CAS/SAFEA International Partnership Program for Creative Research Teams.

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Author notes

  1. Zihui Ma and Wei Li contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China

    Zihui Ma, Wei Li, Peng Zhang, Haining Lyu & Wen-Bing Yin

  2. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China

    Zihui Ma & Wen-Bing Yin

  3. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China

    Youcai Hu

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  1. Zihui Ma
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  2. Wei Li
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Correspondence to Wen-Bing Yin.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Ma, Z., Li, W., Zhang, P. et al. Rational design for heterologous production of aurovertin-type compounds in Aspergillus nidulans . Appl Microbiol Biotechnol 102, 297–304 (2018). https://doi.org/10.1007/s00253-017-8606-9

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  • DOI: https://doi.org/10.1007/s00253-017-8606-9

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