4 September 2015

Amyris Achieves Breakthrough Performance With 2nd Fragrance Molecule Ready for Industrial Scale Fermentation in Less Than 12 Months

Unprecedented Speed of Microbial Engineering Enabled by HI-RYSE™ Genome Engineering Technology

EMERYVILLE, Calif., Aug. 31, 2015 — Amyris, Inc. (Nasdaq:AMRS), the industrial bioscience company, announced today that it has developed a yeast strain ready to produce a new fragrance molecule at commercial scale in less than 12 months from the start of strain engineering, and plans to begin manufacturing of this molecule in September at its Brotas production facility. The engineered strain was designed, engineered, optimized and scaled for industrial fermentation using Amyris’s advanced synthetic biology platform, showcasing the company’s proprietary HI-RYSE™ (Hyper-Integration for Rapid Yeast Strain Engineering) technology. This achievement adds to the growing number of successfully-scaled molecules produced by Amyris for its partners and consumers, which find use in wide-ranging products such as pharmaceuticals, fuels and specialty chemicals, and are made from renewable plant-based feedstock.

An infographic accompanying this release is available at http://media.globenewswire.com/cache/19847/file/36826.pdf

“To deliver on our customers’ expectations of lower cost, better performing chemistry for industrial applications, we needed a technology that could perform faster than one-step-at-a-time engineering as you see with current technologies like CRISPR, which limits the speed of product development,” said John Melo, President and CEO of Amyris. “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. 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.”

“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 and one of the world’s leading geneticists, as well as an advisor 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.”

HI-RYSE™ Technology: Fast Genome Engineering for Faster Product Development

Core to Amyris’s industrial synthetic biology platform is its HI-RYSE Genome Engineering Technology, which is the subject of United States Patent No. 8,685,737 (“Methods for Genomic Modification”).1 HI-RYSE utilizes site-specific nucleases (DNA cleavage enzymes) to facilitate the simultaneous targeted integration of multiple DNA inserts into a host cell’s genome in a single reaction. This obviates iterative engineering steps and the need for selectable markers, dramatically reducing the time needed to optimize the cell to produce a desired molecule. In particular, HI-RYSE enables high-efficiency installation of entire biosynthetic pathways, as well as pathway enhancements that serve to significantly boost the transformation of carbon from renewable feedstock, such as sugar cane, into target molecules via microbial fermentation. Moreover, HI-RYSE is compatible with any nuclease capable of specifically targeting DNA sequences, such as meganucleases, Zinc Finger Nucleases (ZFNs), and Transcription activator-like effector nucleases (TALENs).

Successful Adaptation of HI-RYSE to CRISPR/Cas9

In research performed under an award from the Defense Advanced Research Projects Agency (DARPA)2, Amyris has also successfully demonstrated the adaptation of HI-RYSE to the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR-associated (Cas) nuclease system, the results of which have been published in the inaugural issue of Cell Systems (Horwitz, Walter et. al., Efficient Multiplexed Integration of Synergistic Alleles and Metabolic Pathways in Yeasts via CRISPR-Cas, Cell Systems 1, 88-96 (2015)).3 This publication highlights the achievement of simultaneous genomic integration of an 11-gene, 24-kb biosynthetic pathway for a building block molecule to industrially important 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.4

 

About Amyris

Amyris is the integrated renewable products company that is enabling the world’s leading brands to achieve sustainable growth. Amyris applies its innovative bioscience solutions to convert plant sugars into hydrocarbon molecules, specialty ingredients and consumer products. The company is delivering its No Compromise® products in focused markets, including specialty and performance chemicals, fragrance ingredients, and cosmetic emollients. More information about the company is available at www.amyris.com.

Amyris, the Amyris logo, HI-RYSE, and No Compromise are trademarks or registered trademarks of Amyris, Inc. All other trademarks are the property of their respective owners.

 

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=8,685,737&OS=8,685,737&RS=8,685,737

2 DARPA Living Foundries, Agreement # HR0011-12-3-0006. See also: http://investors.amyris.com/releasedetail.cfm?releaseid=682277

3 http://www.cell.com/cell-systems/abstract/S2405-4712%2815%2900003-4

4 See International Patent Application Publication No. WO/2015/095804: https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2015095804&recNum=5&maxRec=329&office=&prevFilter=&sortOption=Pub+Date+Desc&queryString=FP%3A%28Amyris%29&tab=PCT+Biblio

Source: Amyris, press release, 2015-08-31.

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