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Title: Protein hyperproduction in fungi by design

Abstract

The secretion of enzymes used by fungi to digest their environment has been exploited by humans for centuries for food and beverage production. More than a century after the first biotechnology patent, we know that the enzyme cocktails secreted by these amazing organisms have tremendous use across a number of industrial processes. Secreting the maximum titer of enzymes is critical to the economic feasibility of these processes. So far, traditional mutagenesis and screening approaches have generated the vast majority of strains used by industry for the production of enzymes. Until the emergence of economical next generation DNA sequencing platforms, the majority of the genes mutated in these screens remained uncharacterized at the sequence level. In addition, mutagenesis comes with a cost to an organism’s fitness, making tractable rational strain design approaches an attractive alternative. As an alternative to traditional mutagenesis and screening, controlled manipulation of multiple genes involved in processes that impact the ability of a fungus to sense its environment, regulate transcription of enzyme-encoding genes, and efficiently secrete these proteins will allow for rational design of improved fungal protein production strains.

Authors:
ORCiD logo [1]
  1. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biosystems Design and Simulation Group, Environmental Molecular Sciences Division and Earth and Biological Sciences Directorate
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1463032
Alternate Identifier(s):
OSTI ID: 1468613; OSTI ID: 1513534
Report Number(s):
PNNL-SA-137094
Journal ID: ISSN 0175-7598; PII: 9265
Grant/Contract Number:  
AC0576RL01830; AC02-05CH11231; AC05-76RL01830
Resource Type:
Published Article
Journal Name:
Applied Microbiology and Biotechnology
Additional Journal Information:
Journal Volume: 102; Journal Issue: 20; Journal ID: ISSN 0175-7598
Publisher:
Springer
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Enzyme; Protein; Hyperproduction; Secretion; Biodesign; Fungi; Biotechnology; Enzyme, Protein, Hyperproduction, Secretion, Biodesign, Fungi, Biotechnology

Citation Formats

Baker, Scott E. Protein hyperproduction in fungi by design. United States: N. p., 2018. Web. doi:10.1007/S00253-018-9265-1.
Baker, Scott E. Protein hyperproduction in fungi by design. United States. https://doi.org/10.1007/S00253-018-9265-1
Baker, Scott E. Sat . "Protein hyperproduction in fungi by design". United States. https://doi.org/10.1007/S00253-018-9265-1.
@article{osti_1463032,
title = {Protein hyperproduction in fungi by design},
author = {Baker, Scott E.},
abstractNote = {The secretion of enzymes used by fungi to digest their environment has been exploited by humans for centuries for food and beverage production. More than a century after the first biotechnology patent, we know that the enzyme cocktails secreted by these amazing organisms have tremendous use across a number of industrial processes. Secreting the maximum titer of enzymes is critical to the economic feasibility of these processes. So far, traditional mutagenesis and screening approaches have generated the vast majority of strains used by industry for the production of enzymes. Until the emergence of economical next generation DNA sequencing platforms, the majority of the genes mutated in these screens remained uncharacterized at the sequence level. In addition, mutagenesis comes with a cost to an organism’s fitness, making tractable rational strain design approaches an attractive alternative. As an alternative to traditional mutagenesis and screening, controlled manipulation of multiple genes involved in processes that impact the ability of a fungus to sense its environment, regulate transcription of enzyme-encoding genes, and efficiently secrete these proteins will allow for rational design of improved fungal protein production strains.},
doi = {10.1007/S00253-018-9265-1},
journal = {Applied Microbiology and Biotechnology},
number = 20,
volume = 102,
place = {United States},
year = {2018},
month = {8}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1007/S00253-018-9265-1

Citation Metrics:
Cited by: 8 works
Citation information provided by
Web of Science

Figures / Tables:

Fig. 1 Fig. 1: Manipulation of genes that encode proteins involved in regulating nutrient sensing, transcription, translation, and secretion is key for rational design of fungal lignocellulosic deconstruction enzyme hypersecretors

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Long-term strain improvements accumulate mutations in regulatory elements responsible for hyper-production of cellulolytic enzymes
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Forward genetics screen coupled with whole-genome resequencing identifies novel gene targets for improving heterologous enzyme production in Aspergillus niger
journal, January 2018

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Restoration of female fertility in Trichoderma reesei QM6a provides the basis for inbreeding in this industrial cellulase producing fungus
journal, September 2015

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The importance of connections between the cell wall integrity pathway and the unfolded protein response in filamentous fungi
journal, July 2014

  • Malavazi, I.; Goldman, G. H.; Brown, N. A.
  • Briefings in Functional Genomics, Vol. 13, Issue 6
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Carbon catabolite repression in plant pathogenic fungi: isolation and characterization of the Gibberella fujikuroi and Botrytis cinerea creA genes
journal, March 2000


Regulators of plant biomass degradation in ascomycetous fungi
journal, June 2017

  • Benocci, Tiziano; Aguilar-Pontes, Maria Victoria; Zhou, Miaomiao
  • Biotechnology for Biofuels, Vol. 10, Issue 1
  • DOI: 10.1186/s13068-017-0841-x

The low affinity glucose transporter HxtB is also involved in glucose signalling and metabolism in Aspergillus nidulans
journal, March 2017

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Properties of the hexose transport systems of Aspergillus nidulans
journal, October 1971

  • Mark, Cynthia G.; Romano, Antonio H.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 249, Issue 1
  • DOI: 10.1016/0005-2736(71)90098-8

Omics Analyses of Trichoderma reesei CBS999.97 and QM6a Indicate the Relevance of Female Fertility to Carbohydrate-Active Enzyme and Transporter Levels
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Synergistic and Dose-Controlled Regulation of Cellulase Gene Expression in Penicillium oxalicum
journal, September 2015


Activation mechanisms of the HACI-mediated unfolded protein response in filamentous fungi: M. Saloheimo, M. Valkonen and M. Penttillä
journal, February 2003


Deciphering the Regulatory Network between the SREBP Pathway and Protein Secretion in Neurospora crassa
journal, April 2017


Control of yeast GAL genes by MIG1 repressor: a transcriptional cascade in the glucose response.
journal, November 1991


Carbon Catabolite Repression of Gene Expression and Conidiation inNeurospora crassa
journal, October 1998


Comparative Genomics Analysis of Trichoderma reesei Strains
journal, December 2013

  • Koike, Hideaki; Aerts, Andrea; LaButti, Kurt
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Works referencing / citing this record:

Fungal Biotechnology in Space: Why and How?
book, January 2020


Figures / Tables found in this record:

    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.