Business developments
Catalysis, both chemocatalysis and biocatalysis, is an active area of investment of fine-chemical companies, contract manufacturers,
and technology providers specializing in catalysis. In March 2011, Materia announced plans for a catalyst manufacturing and
research and development facility in Singapore. Materia specializes in olefin-metathesis catalyst technology based on the
work of Robert Grubbs, professor at the California Institute of Technology, the 2005 Nobel Laureate for Chemistry, and a member
of Materia's scientific advisory board and board of directors. Olefin-metathesis technology is used in fine-chemical manufacture
and in other industrial chemical sectors.
Materia expects to complete the site-selection process in the third quarter of 2011 and begin construction by the end of the
year. The facility will have initial operating capacity of 10 metric tons by the end of 2012. In addition to catalyst manufacturing,
the plant will house research, development, and technical-service resources. Earlier this year, Materia received a $17-million
investment by a group of private investors.
The contract development and manufacturing organization (CDMO) Almac is expanding its biocatalysis business with a $4-million
investment for discovering new biocatalytic platforms and for other research areas. These areas include hyperactivation of
biocatalysts to reduce enzyme loadings, drivers for cofactor recycles, and resolving problems with equilibriums. In 2009,
Almac launched carbonyl reductase, transaminase, hydrolase, nitrilase, and nitrile hydratase enzyme-screening kits. In adddition
to screening kits, the company offers services for enzyme-screening kits and custom transformations, and supply of chiral
intermediates.
In January 2011, Codexis formed a biocatalysis collaboration with Dainippon Sumitomo Pharma (DSP). Under the agreement, Codexis
is supplying biocatalysis-screening products and services to DSP for use in selected undisclosed therapeutic products in DSP's
development pipeline. Also, in January 2011, Codexis and DSM Pharmaceutical Products, the custom-manufacturing organization
of Royal DSM, formed an enzyme-supply agreement. The agreement grants DSM rights to use Codexis' custom biocatalysts and services
and secures supply of Codexis enzymes for commercialization of pharmaceutical manufacturing routes developed by the InnoSyn
route-scouting services of DSM. In early 2010, Codexis formed two separate pacts for applying its biocatalyst technology for
two other CDMOs, Ampac Fine Chemicals and Dishman Chemical and Pharmaceuticals, for their use in manufacturing intermediates
and APIs.
Codexis recently worked with Merck & Co. to develop an enzymatic process to make sitagliptin, which is the active ingredient
in Merck's Januvia. The process improvements in the sitagliptin synthesis were recognized by the US Environmental Protection
Agency's 2010 Presidential Green Chemistry Challenge Awards. The earlier manufacturing process involved an asymmetric catalytic
hydrogenation of an unprotected enamine, but had some challenges, including inadequate stereoselectivity that required a crystallization
step and high-pressure hydrogenation (at 250 psi) that required the use of a rhodium catalyst (7).
Collaboration between Merck and Codexis led to an improved, greener route for the manufacture of sitagliptin. Starting from
an R-selective transaminase, with some slight activity on a smaller, truncated methyl ketone analog of the sitagliptin ketone,
Codexis evolved a biocatalyst to enable a new manufacturing process to supplant the hydrogenation route. The evolved transaminase
had a compounded improvement in biocatalytic activity of more than 25,000-fold, with no detectable amounts of the undesired,
S-enantiomer of sitagliptin being formed. The streamlined, enzymatic process eliminated the high-pressure hydrogenation, metal
catalysts (i.e., rhodium and iron), and the chiral purification step. The benefits of the new process included a 56% improvement
in productivity, a 10–13% overall increase in yield, and a 19% reduction in overall waste generation (7).
In October 2010, Codexis expanded its portfolio of screening kits to include two commonly used enzyme classes, ketoreductase
and transaminase enzymes. The company also entered its panels for ketoreductase biocatalysts for producing chiral secondary
alcohols, which are used as intermediates in asymmetric API synthesis, for consideration in EPA's 2010 green chemistry awards.
Codexis developed processes for chiral alcohol intermediates of four generic APIs with variants identified from its KRED (i.e.,
ketoreductase) panel screens. Codexis also has other enzyme panels of transaminase, nitrilase, acylase, halohydrin dehalogenase,
and "ene" reductase biocatalysts.
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