Amyris starts fermentation plant in Brazil

I have not covered Amyris as much as I would like to in the past few years as the company is more focused on highly-specialised chemicals compared to the products I typically cover for Tecnon OrbiChem’s monthly Bio-Materials report.

However, it is interesting to hear that the company has finally started its new precision fermentation plant in Barra Bonita, Brazil which will produce natural vanillin, sugarcane-based Reb M, squalene, squalene, hemisqualene and patchouli along with other molecules. The plant will reportedly allow Amyris to more efficiently meet demand from its ingredient customers after several years of operating under third-party capacity supply constraints. Capacity of this new facility was not disclosed in the press release although I’ve seen some information from Amyris stating the fermentation capacity at around 1.44 million litres annually at full scale with five self-contained lines for diverse molecule production.

Amyris started its operations in the USA via toll manufacturing with Tate & Lyle in Decatur, Illinois, before moving its production to Brotas, Brazil operated by Amyris Brasil Ltda. The Brotas, Brazil facility was adjacent to an existing sugar and ethanol mill. The facility has a capacity of 12 ktpa (six 200,000 litre production fermenters designed to process sugarcane juice and syrup from up to 1 million tons of raw sugarcane annually).  DSM acquired Amyris Brasil Ltda. in late 2017 for $58 million and the establishment of a long-term manufacturing partnership for Amyris’ high-volume products including off-take of farnesene. The deal included an additional value share arrangement over a 3-year period amounting to $37.5m. The strategic alliance between DSM and Amyris started in May 2017 with an equity investment of $25m by DSM in Amyris in return for a 12% stake and a seat on the board. In August 2017, Amyris received another $25m from DSM and a second seat on the board. Since then the alliance has expanded with several significant product development collaborations including vitamin A and other nutritional ingredients.

On March 31, 2021, Amyris and DSM entered a license agreement and asset purchase agreement where DSM acquired exclusive rights to Amyris’s Flavor and Fragrance (F&F) product portfolio. DSM also acquired Amyris’s F&F finished goods inventory on-hand, unbilled accounts receivables and billed accounts receivable that were uncollected at closing. Amyris and DSM also entered into a 15-year manufacturing agreement where Amyris will manufacture certain F&F ingredients for DSM to supply to third parties. With DSM now merged with Firmenich, I do wonder if there will be further changes to the Amyris-DSM relationship given that Amyris have also been collaborating with other F&F majors such as IFF, Takasago and Givaudan.

In 2016, Amyris signed an MOU with CJ Cheiljedang for the manufacture of farnesene at CJ’s existing facilities while in 2017, Amyris, announced an agreement with Phyto Tech Corp (doing business as Blue California) where it will provide access to its fermentation manufacturing in China and provide the necessary capital to produce Amyris’s No Compromise® ingredients based from farnesene. Blue California is based in southern California and is a major producer of food, flavour and fragrance ingredients and nutraceuticals. Antibióticos de Leon (ADL Biopharma) was one of the first contract manufacturing organisations that Amyris has used to successfully produce farnesene. In 2018, Amyris expanded its contract manufacturing deal with ADL Biopharma. As I’ve said, I have not been following Amyris closely and therefore I don’t know if these production contracts are still ongoing. Amyris announced its manufacturing plans for Barra Bonita around 2019.

Amyris also has pilot and demonstration-scale facilities in Campinas, Brazil, a pilot-scale production facility at its headquarters in Emeryville, California, and a commercial-scale production facility in Leland, North Carolina (which is part of the Aprinnova joint venture).

As far as I know, Amyris is currently the only known commercial-scale producer of renewable farnesene in the world. The company has developed a proprietary pathway for high-level production of trans-β-farnesene from sugars via yeast fermentation, which requires genetic transformation of S. cerevisiae with advanced strain engineering technologies. In the mevalonate pathway in the yeast cell, acetyl coA (produced from the metabolism of glucose) is converted into isopentyl diphosphate (IPP) which is further transformed into farnesyl diphosphate (FPP) and C15 isoprenoids. According to Amyris, it is able to use a wide variety of feedstocks for production but has focused on accessing Brazilian sugarcane for its large-scale production because of its renewability, low cost and relative price stability.

During my first few years of coverage about Amyris, I remember the company has already been developing its farnesene-based fragrance molecules in a multi-year collaboration with IFF, Firmenich, Givaudan and Takasago. Amyris’s product portfolio including other farnesene-based ingredients, fermentation-based squalene and other molecules is continuously being developed with various partners across various industries including cosmetics, personal care, nutrition, flavours and fragrances as well as fermentation-based commodity chemicals, rubber, based oils, lubricants, adhesives, fuel, etc.

In 2015, the company sold a 50% stake of its Neossance® farnesene-based squalene business to Japan-based cosmetic specialty chemical provider, NIKKOL Group, for a purchase price of up to $20 million in total. The Neossance® JV with NIKKOL is called Apprinova.  American Refining Group (ARG), Chevron and H&R Group US Inc., meanwhile, all committed equity stakes in Novvi LLC, a joint venture of Amyris which produces base oils and lubricants made from Amyris’s sugar-based farnesene.  As of 31 December 2021, Chevron owned 64.3% of Novvi LLC.

In 2021, Ingredion purchased 31% stake in RealSweet LLC, a 100% owned subsidiary of Amyris. RealSweet manufactures and sells Amyris’s zero-calorie, fermentation-derived Reb M sweetener. The $100 million deal also includes an exclusive license to sell and market Reb and a minority stake in the Barra manufacturing facility. Amyris will earn a profit share from Reb M sales.

Back to the Barra facility, the site is said to be strategically located next to the Raizen sugar mill, which is the second-largest Bonsucro-certified sugar mill in the world. The facility will have sustainably generated electricity and will use biogas supply starting in 2024. The site reportedly has ample space and infrastructure for future expansion.