Industrial bioscience company, Amyris, Inc. announced the development of a yeast strain ready to produce a new fragrance molecule at commercial scale in less than 12 months from the start of strain engineering.
Utilizing Amyris’s synthetic biology platform and manufactured at the Brotas production facility, the engineered strain was designed for industrial fermentation to exhibit Aammyris’s HI-RYSE (Hyper-Integration for Rapid Yeast Strain Engineering) technology.
The HI-RYSE Genome Engineering Technology—subject of the United States Patent No. 8,685,737—utilizes site-specific nucleases to facilitate the simultaneous targeted integration of multiple DNA inserts into a host cell’s genome in a single reaction.
“Our patented HI-RYSE technology has enabled us to deliver this fragrance molecule to our collaboration partner in half the time we expected and at a lower production cost than we planned,” said John Melo, president and CEO of Amyris. “This is a major breakthrough for industrial biotechnology that will enable us to accelerate the commercialization of the 17 molecules currently under contract for development in our collaboration portfolio. At maturity, we expect each of these molecules to deliver $30 million to $40 million of annual product revenue at approximately a 60% gross margin.”
HI-RYSE is compatible with any nuclease and is capable of targeting DNA sequences specifically, which reduces time to optimize the cell to produce a desired molecule. With high efficient installation of biosynthetic pathways, HI-RYSE boosts carbon to renewable feedstock, such as sugar cane, into target molecules through microbial fermentation.
“With our HI-RYSE technology, we’ve combined the precision of site-specific genome engineering with the speed of high-throughput multiplexing, which is enabling Amyris to produce new molecules essentially on demand,” said Joel Cherry, president of Research & Development at Amyris. “This is a milestone in industrial bioscience not unlike the advent of industrialized travel – we’re now riding by railway where there were only wagons before.”
“Amyris’s technology platform is well suited to combine high-speed genomic engineering with high-performance screening and scaling to set the bar for industrial biotechnology applications,” said David Botstein Ph.D., professor Emeritus (Genomics) at Princeton University, geneticist and adviser to Amyris. “Bio-based molecules for any application imaginable are very quickly moving from conception to reality, and the expertise and advanced strain engineering capabilities of Amyris positions them to be a leader to move this field forward.”
Amyrise also showcased the adaptation of HI-RYSE to the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR-associated (Cas) nuclease system, which achieves simultaneous genomic integration of an 11-gene, 24-kb biosynthetic pathway for a building block molecule to industrial bioplastics such as nylon, polyurethane and polyethylene terephthalate (PET). This resulted in the single-step conversion of a wild-type yeast to a yeast producing 2.7 g/L of a precursor molecule. Further application of this technique to a mammalian genome (cultured human 293T cells) resulted in a greater than 2-fold increase in incorporation of exogenous DNA into a genomic target site, compared to a standard CRISPR/Cas9 protocol.
According to Melo, similarly to CRISPR’s limited speed of product development, HI-RYSE also meets lower costs, better performing chemistry for industrial applications and performs faster than one-step-at-a-time engineering.