Photosynthetic Harvest Milks Green Plants for Human, Microbial Proteins
They don't call them pharmaceutical plants for nothing. Plants—the green kind—were once the starting points for about 80% of all pharmaceuticals. During the 19th century, leaves, bark, stems, and roots were routinely harvested and processed, in brick-and-mortar plants, to produce lotions, powders, tablets, and elixirs that lined the shelves of apothecaries. Even today such highly processed products as codeine begin their existence in poppy fields.
With the advent of genetic engineering it's now possible to coax plants into producing pharmaceutical-grade products that nature never intended them to make. Which is why Phytomedics Inc. (Willingboro, NJ) believes there may be a pharmaceutical "plant" in your future. Phytomedics uses its proprietary Rhizosecretion technology to "milk" green plants for a variety of human and microbial proteins. Rhizosecretion, developed by Ilya Raskin at Rutgers University (New Brunswick, NJ) and exclusively licensed to Phytomedics, takes advantage of the ability of green plants grown in water (hydroponically), to synthesize and secrete large quantities of bioactive compounds from their roots. Using genetic material from humans, jellyfish, and microbes, Phytomedics scientists have engineered the roots of plants to produce and exude large quantities of recombinant proteins, continuously, into a hydroponic medium.
Recombinant proteins are widely used as pharmaceuticals and as industrial and food processing enzymes. While the need for recombinant proteins is increasing each year, the growth of the market is limited, due to the relatively high costs of protein manufacture using conventional microbial and animal cell culture systems. Protein manufacture using Rhizosecretion offers a low cost, large-scale recombinant protein production system with simplified downstream processing.
According to Ira Pastor, director of business development for Phytomedics, his company is now optimizing a molecular farming system capable of continuously secreting recombinant proteins without the need to destroy the actual plant material, as is the case with other transgenic plant protein production systems. "We are also developing methods for increasing protein yield during the scale-up production process, such that the protein secreting plants can be indefinitely propagated from seeds or cuttings at a very low cost," Pastor said. "We are now initiating collaborations with industrial partners to jointly proceed with further development of the technology for a wide range of commercial applications."
Harvesting, Discovery Technology
Phytomedics has two harvesting techniques under development, both falling into a general category known as "phytosecretion." Rhizosecretion, described above, exploits a green plant's ability to exude large quantities of organic compounds and proteins from its roots into a simple aqueous medium. Rhizosecretion is currently used to manufacture bioactive compounds identified in the RhizEx libraries and to produce recombinant proteins from tobacco and tomato.
Phyllosecretion exploits leaf guttation as a medium to continuously wash recombinant proteins away from a living plant. Guttation fluid, commonly known as "dew," is exuded by a plant every morning and can be transformed into a concentrated solution of recombinant proteins.
In addition to research into recombinant protein biomanufacturing, PHI has developed a broad range of integrated life science biotechnologies for applications such as pharmaceutical and agrichemical discovery, gene amplification for crop engineering, bioactive peptide development, and production of scientifically optimized nutraceuticals.
One such technology are RhizEx libraries—proprietary mixtures of structurally novel natural products produced and/or secreted by hydroponically cultivated plant roots exposed to various stresses (elicitors). Currently, the libraries include elicited and non-elicited root extracts (elicidates) and exudates of 600 plant species belonging to at least 150 families (approx. 3400 samples). RhizEx samples scored a remarkable 20% hit rates in several internal anti-microbial and crop protection assays. Hit rates for conventional plant extracts usually do not exceed 1–2%, and are mainly produced by well known compounds with no commercial potential.
Phytomedics' proprietary elicitation process is the key to novelty, diversity, and bio-activity of RhizEx libraries. By mimicking various biological and environmental stresses, elicitation triggers the production of bio-active natural products absent under normal conditions. PMI has demonstrated that elicitation adds another dimension to the chemodiversity of plant natural products, greatly increasing the chances of finding novel lead compounds.
A major advantage of RhizEx libraries is that any lead compound contained in the libraries can be efficiently manufactured on a small or large-scale using rhizosecretion or phyllosecretion, thus guaranteeing re-supply of an active ingredient in large quantities.
For more information: Ira Pastor, Director for Business Development, Phytomedics Inc., Hill International Building, Suite 3, One Levitt Parkway, Willingboro, NJ 08046. Tel: 609-835-1600, ext. 1. Email: ipastor@phiroots.com.
To learn about Rhizosecretion: Ilya Raskin, Professor, Rutgers University Biotechnology Center, Foran Hall, Cook College, 59 Dudley Rd., New Brunswick, NJ 08901-8520. Tel.: 732-932-8734, ext. 227. Email: raskin@aesop.rutgers.edu.
By Angelo DePalma