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Structural Variation among Wild and Industrial Strains of Penicillium chrysogenum

Wong, Valerie L. and Ellison, Christopher E. and Eisen, Michael B. and Pachter, Lior and Brem, Rachel B. (2014) Structural Variation among Wild and Industrial Strains of Penicillium chrysogenum. PLoS ONE, 9 (5). Art. No. e96784. ISSN 1932-6203. PMCID PMC4019546.

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Strain selection and strain improvement are the first, and arguably most important, steps in the industrial production of biological compounds by microorganisms. While traditional methods of mutagenesis and selection have been effective in improving production of compounds at a commercial scale, the genetic changes underpinning the altered phenotypes have remained largely unclear. We utilized high-throughput Illumina short read sequencing of a wild Penicillium chrysogenum strain in order to make whole genome comparisons to a sequenced improved strain (WIS 54–1255). We developed an assembly-free method of identifying chromosomal rearrangements and validated the in silico predictions with a PCR-based assay and Sanger sequencing. Despite many rounds of mutagen treatment and artificial selection, WIS 54–1255 differs from its wild progenitor at only one of the identified rearrangements. We suggest that natural variants predisposed for high penicillin production were instrumental in the success of WIS 54–1255 as an industrial strain. In addition to finding a previously published inversion in the penicillin biosynthesis cluster, we located several genes related to penicillin production associated with these rearrangements. By comparing the configuration of rearrangement events among several historically important strains known to be high penicillin producers to a collection of recently isolated wild strains, we suggest that wild strains with rearrangements similar to those in known high penicillin producers may be viable candidates for further improvement efforts.

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Eisen, Michael B.0000-0002-7528-738X
Pachter, Lior0000-0002-9164-6231
Additional Information:© 2014 Wong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: November 30, 2013; Accepted: April 11, 2014; Published: May 13, 2014. The authors have no support or funding to report. Competing interests: MBE is a member of the PLOS Board of Directors. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. Devin Scannell produced the genomic libraries for sequencing. Daniel Henk graciously provided strains. We thank two reviewers for their helpful comments. Author Contributions: Conceived and designed the experiments: VLW CEE RBB. Performed the experiments: VLW CEE. Analyzed the data: VLW CEE. Contributed reagents/materials/analysis tools: VLW CEE MBE LP RBB. Wrote the paper: VLW CEE RBB. Supervised the research: MBE LP RBB.
Issue or Number:5
PubMed Central ID:PMC4019546
Record Number:CaltechAUTHORS:20190507-112223935
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Official Citation:Wong VL, Ellison CE, Eisen MB, Pachter L, Brem RB (2014) Structural Variation among Wild and Industrial Strains of Penicillium chrysogenum. PLoS ONE 9(5): e96784.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95302
Deposited By: Tony Diaz
Deposited On:07 May 2019 18:31
Last Modified:03 Oct 2019 21:12

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