Plants are a vast renewable source of important natural products, and the development of genetic engineering techniques has opened up a myriad of new possibilities for extending the biosynthetic capabilities of plants. Examples include the production of heterologous proteins and new metabolic pathways in whole plants, harvested plant tissues, and <i>in vitro</i> systems such as plant cell cultures in bioreactors.  Although plant biotechnology has been deployed commercially for decades for improved agronomic traits of crops, the combination of new plant expression technologies and synthetic biology components, inexpensive DNA synthesis, and novel bioprocessing strategies are enabling plants and plant cells to be used as molecular foundries.  For example, new production platforms based on transient expression in nontransgenic plants within contained manufacturing facilities are showing enormous promise for rapid, scalable, and lower cost production of vaccines and therapeutics.  Plants are unique higher eukaryotic production hosts that can be very simply grown using light, water, carbon dioxide, and mineral nutrients. They not only serve as a “single use disposable bioreactor” but are completely biodegradable/recyclable and linearly scalable.  In addition, plant cell suspension cultures grown in bioreactors are an alternative to more well-developed bioproduction systems using bacterial, yeast, mammalian, and insect cell cultures. Although the first FDA-approved human therapeutic made in plant cell culture was introduced just ten years ago (Elelyso<sup>TM</sup> made in transgenic carrot cultures), plant cell culture offers a number of advantages: simple, chemically-defined, low cost animal component-free medium, the ability to produce complex glycoproteins, potential for long-term operation, and inability to propagate mammalian viruses.  However, these systems are not without their own challenges. This presentation will describe some of the unique challenges encountered when using plants as molecular foundries, as well as our group’s research over the years to increase productivity, product quality, and production speed, with applications ranging from medical countermeasures for biodefense on Earth to molecular pharming on Mars.

2022 DIC Wang award lecture: Plants as molecular foundries:  From earth to deep space

ACS Spring 2022

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