Reviving natural product and drug discovery pipelines with fungal artificial chromosome (FAC) technology

Kenneth Clevenger, Jin Woo Bok, Rosa Ye, Galen Miley, Thomas Velk, Cynthia Chen, Ka Houa Yang, Peng Gao, Matthew Lamprecht, Paul Martin Thomas, Md Nurul Islam, Nancy Keller, Neil L Kelleher, Chengcang Wu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

We have developed the fungal artificial chromosome [FAC, or autonomously replicating E. coli-fungal shuttle bacterial artificial chromosome (BAC)] technology. The FAC system or technology enables unbiased capturing of 263 full-length large secondary metabolite (SM) gene clusters (each lOOkb or larger) as individual FAC clones, from 6 sequenced fungal genomes for one-step transformation and heterologous expression. The FAC technology also enables precise SM gene and gene cluster editing and activating silent and cryptic SM gene clusters. We have demonstrated that the FAC technology is extremely effective for natural product and drug discovery by using a liquid chromatography-fourier transform mass spectrometer (LC-FTMS) with novel data analysis pipeline. This novel FAC platform provides a major advance in the study of fungal biosynthesis, enabling rapid detection of novel SMs, identification of their biosynthetic machinery, and dissection of their biosynthesis. As an example, three SM compounds: benzomalvin A, ophiobolin G, and a novel lipopeptide has been discovered from a FAC clone: AtFAC9J20 containing a super-SM gene cluster. This disruptive technology could revive natural product and drug discovery platform from sequenced fungi, fungal metagenomes and environmental microbial metagenomes.

Original languageEnglish (US)
Title of host publicationBiotech, Biomaterials and Biomedical - TechConnect Briefs 2016
PublisherTechConnect
Pages226-227
Number of pages2
Volume3
ISBN (Electronic)9780997511727
StatePublished - Jan 1 2016
Event10th Annual TechConnect World Innovation Conference and Expo, Held Jointly with the 19th Annual Nanotech Conference and Expo, and the 2016 National SBIR/STTR Conference - Washington, United States
Duration: May 22 2016May 25 2016

Other

Other10th Annual TechConnect World Innovation Conference and Expo, Held Jointly with the 19th Annual Nanotech Conference and Expo, and the 2016 National SBIR/STTR Conference
CountryUnited States
CityWashington
Period5/22/165/25/16

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Keywords

  • Drug discovery
  • Fungal artificial chromosome (FAC)
  • Natural product
  • Secondary metabolite (SM) gene clusters

ASJC Scopus subject areas

  • Fluid Flow and Transfer Processes
  • Biotechnology
  • Surfaces, Coatings and Films
  • Fuel Technology

Cite this

Clevenger, K., Bok, J. W., Ye, R., Miley, G., Velk, T., Chen, C., Yang, K. H., Gao, P., Lamprecht, M., Thomas, P. M., Islam, M. N., Keller, N., Kelleher, N. L., & Wu, C. (2016). Reviving natural product and drug discovery pipelines with fungal artificial chromosome (FAC) technology. In Biotech, Biomaterials and Biomedical - TechConnect Briefs 2016 (Vol. 3, pp. 226-227). TechConnect.