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Apc.LaeA and Apc.VeA of the velvet complex govern secondary metabolism and morphological development in the echinocandin-producing fungus Aspergillus pachycristatus

  • Nan Lan
  • Qun Yue
  • Zhiqiang An
  • Gerald F. BillsEmail author
Genetics and Molecular Biology of Industrial Organisms - Original Paper

Abstract

The impact of the global secondary metabolite regulators LaeA and VeA on echinocandin B production and morphological development was evaluated in the industrial production strain Aspergillus pachycristatus NRRL 11440. Other representative secondary metabolites were examined as well to determine if the velvet complex functions as in A. nidulans and other species of fungi. Genetic methods used for gene manipulations in A. nidulans were applied to A. pachycristatus. Separate deletions of genes Apc.laeA and Apc.veA resulted in similar yet differing phenotypes in strain NRRL 11440. Disruption of Apc.laeA and Apc.veA significantly reduced, but did not eliminate, the production of echinocandin B. Similar to what has been observed in A. nidulans, the production of sterigmatocystin was nearly eliminated in both mutants. Quantitative reverse transcription PCR analyses confirmed that selected genes of both the echinocandin B and sterigmatocystin gene clusters were down-regulated in both mutant types. The two mutants differed with respect to growth of aerial hyphae, pigmentation, development of conidiophores, conidial germination rate, and ascospore maturation. Further functional annotation of key regulatory genes in A. pachycristatus and related Aspergillus species will improve our understanding of regulation of echinocandin production and co-produced metabolites.

Keywords

Antifungal Eurotiales Fermentation Nonribosomal peptide synthetase Sterigmatocystin 

Notes

Acknowledgements

This work was supported by Cidara Therapeutics, Inc. Yan Li assisted in setting up HPLC–MS calibration curves. We thank the USDA NRRL Culture Collection for supply of strain 11440 and Philipp Weimann for helpful comments on the draft manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. The opinions expressed in this article are solely those of the authors and are independent of those of Cidara Therapeutics, Inc.

Supplementary material

10295_2019_2250_MOESM1_ESM.pdf (1.3 mb)
Supplementary material 1 (PDF 1323 kb)

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2019

Authors and Affiliations

  1. 1.Texas Therapeutics Institute, The Brown Foundation Institute of Molecular MedicineThe University of Texas Health Science Center at HoustonHoustonUSA
  2. 2.Biotechnology Research InstituteChinese Academy of Agricultural SciencesBeijingChina

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