skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Cells as Biofactories: Parallels Between Biopharmaceutical Manufacturing and Industrial Biotechnology
Industrial biotechnology and biopharmaceutical manufacturing leverage biology to enable cellular systems to serve as factories to produce molecules of value to humankind. These biotechnological processes utilize diverse host organisms and address applications from biofuel, polymer building blocks, antibiotics, and whole cell therapies. Industrial biotechnology can address environmental and sustainability goals in addition to chemical production. In a similar fashion, the field of biopharmaceutical manufacturing has and continues to produce life-saving medicines. Despite these diverse applications, these fields rely on common biological themes and require similar approaches for genetic and metabolic engineering as discussed in this review. Through advances in synthetic biology, targeted genetic engineering, DNA sequencing, adaptation and high-throughput screening, industrial biotechnology and biopharmaceutical manufacturing utilize the same framework for efficient biochemical production which can be leveraged in current and future collaborations to enable rapid innovation.  more » « less
Award ID(s):
2100502
PAR ID:
10522452
Author(s) / Creator(s):
;
Publisher / Repository:
Mary Ann Liebert, Inc
Date Published:
Journal Name:
Industrial biotechnology
ISSN:
1550-9087
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; ; ; (, mBio)
    Ruby, Edward G. (Ed.)
    ABSTRACT A conspicuous roadblock to studying marine bacteria for fundamental research and biotechnology is a lack of modular synthetic biology tools for their genetic manipulation. Here, we applied, and generated new parts for, a modular plasmid toolkit to study marine bacteria in the context of symbioses and host-microbe interactions. To demonstrate the utility of this plasmid system, we genetically manipulated the marine bacteriumPseudoalteromonas luteoviolacea, which stimulates the metamorphosis of the model tubeworm,Hydroides elegans. Using these tools, we quantified constitutive and native promoter expression, developed reporter strains that enable the imaging of host-bacteria interactions, and used CRISPR interference (CRISPRi) to knock down a secondary metabolite and a host-associated gene. We demonstrate the broader utility of this modular system for testing the genetic tractability of marine bacteria that are known to be associated with diverse host-microbe symbioses. These efforts resulted in the successful conjugation of 12 marine strains from the Alphaproteobacteria and Gammaproteobacteria classes. Altogether, the present study demonstrates how synthetic biology strategies enable the investigation of marine microbes and marine host-microbe symbioses with potential implications for environmental restoration and biotechnology. IMPORTANCEMarine Proteobacteria are attractive targets for genetic engineering due to their ability to produce a diversity of bioactive metabolites and their involvement in host-microbe symbioses. Modular cloning toolkits have become a standard for engineering model microbes, such asEscherichia coli, because they enable innumerable mix-and-match DNA assembly and engineering options. However, such modular tools have not yet been applied to most marine bacterial species. In this work, we adapt a modular plasmid toolkit for use in a set of 12 marine bacteria from the Gammaproteobacteria and Alphaproteobacteria classes. We demonstrate the utility of this genetic toolkit by engineering a marinePseudoalteromonasbacterium to study their association with its host animalHydroides elegans. This work provides a proof of concept that modular genetic tools can be applied to diverse marine bacteria to address basic science questions and for biotechnology innovations. 
    more » « less
  2. ; ; (, Biotechnology Journal)
    Abstract Rapidly expanding biopharmaceutical market demands more cost‐effective platforms to produce protein therapeutics. To this end, novel approaches, such as perfusion culture or concentrated fed‐batch, have been explored for higher yields and lower manufacturing costs. Although these new approaches produced promising results, but their wide‐spread use in the industry is still limited. In this study, a dialysis rolled scaffold bioreactor was presented for long‐term production of monoclonal antibodies with reduced media consumption. Media dialysis can selectively remove cellular bio‐wastes without losing cells or produced recombinant proteins. The dialysis process was streamlined to significantly improve its efficiency. Then, extended culture of recombinant CHO cells for 41 days was successfully demonstrated with consistent production rate and minimal media consumption. The unique configuration of the developed bioreactor allows efficient dialysis for media management, as well as rapid media exchange to harvest produced recombinant proteins before they degrade. Taken together, it was envisioned that the developed bioreactor will enable cost‐effective and long‐term large‐scale culture of various cells for biopharmaceutical production. 
    more » « less
  3. ; ; (, Synthetic Biology and Engineering)
    Zeng, A; Yang, ST (Ed.)
    Biomanufacturing with broad applications in various industries is projected to reach a market value of ~30 trillion USD by 2030, accounting for more than one third of the global manufacturing output. Future biomanufacturing of industrial products will use novel synthetic biology tools and advanced bioprocesses to convert abundant biomass and waste resources into value-added products with comparable or superior properties to replace current petroleum-based products, thus enabling circular bioeconomy with affordable energy, economic growth, and innovation in renewable energy and chemicals production. However, biomanufacturing faces many challenges in its development that requires fundamental research in synthetic biology and novel bioprocesses involving multidisciplinary teams and academic-industry partnerships. In particular, aging and lifespan of microbial cells have been largely overlooked in industrial fermentation. Only recently have microbiologists realized that many microorganisms including yeasts (e.g., Saccharomyces cerevisiae) and bacteria (e.g., Escherichia coli) have chronological and replicative life spans which dramatically impact cell viability and longevity. In this article, we will give our perspective on how synthetic biology may contribute to overcoming some challenges facing industrial biotechnology for fuels and chemicals production from renewable sources, highlighting the importance of understanding and regulating microorganism’s lifespan and aging. 
    more » « less
  4. ; (, Current Opinion in Chemical Biology)
    Growing environmental concerns and the urgency to address climate change have increased demand for the development of sustainable alternatives to fossil-derived fuels and chemicals. Microbial systems, possessing inherent biosynthetic capabilities, present a promising approach for achieving this goal. This review discusses the coupling of systems and synthetic biology, to enable the elucidation and manipulation of microbial phenotypes for the production of chemicals that can substitute for petroleum-derived counterparts and contribute to advancing green biotechnology. The integration of artificial intelligence with metabolic engineering to facilitate precise and data-driven design of biosynthetic pathways is also discussed, along with the identification of current limitations and proposition of strategies for optimizing of biosystems, thereby propelling the field of chemical biology towards sustainable chemical production. 
    more » « less
  5. ; ; ; ; ; ; ; ; ; (, Nature Communications)
    Abstract Plant-derived phenylpropanoids, in particular phenylpropenes, have diverse industrial applications ranging from flavors and fragrances to polymers and pharmaceuticals. Heterologous biosynthesis of these products has the potential to address low, seasonally dependent yields hindering ease of widespread manufacturing. However, previous efforts have been hindered by the inherent pathway promiscuity and the microbial toxicity of key pathway intermediates. Here, in this study, we establish the propensity of a tripartite microbial co-culture to overcome these limitations and demonstrate to our knowledge the first reported de novo phenylpropene production from simple sugar starting materials. After initially designing the system to accumulate eugenol, the platform modularity and downstream enzyme promiscuity was leveraged to quickly create avenues for hydroxychavicol and chavicol production. The consortia was found to be compatible with Engineered Living Material production platforms that allow for reusable, cold-chain-independent distributed manufacturing. This work lays the foundation for further deployment of modular microbial approaches to produce plant secondary metabolites. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email