Methanotrophs are bacteria that can use methane as a sole carbon and energy source for growth; however, it wasn’t until 2004 that the first complete genome sequence from an obligate methanotroph, Methylococcus capsulatus (Bath) (which is featured on Calysta’s website) was obtained (Ward et al.). One of the most surprising outcomes of the project, Ward et al. noted in their paper published in PLoS Biology, was evidence suggesting the existence of previously unsuspected metabolic flexibility in M. capsulatus.

Calysta is applying its expertise in biocatalysis, synthetic biology and advanced bioengineering process design to develop bio-based processes (biological gas-to-liquids, BioGTL) that will operate more cheaply and efficiently than chemical processes. Calysta will use proprietary genetic optimization algorithms to enable the efficient development of bacteria which can convert methane to a variety of alkane fuels.

The company was formed in 2011 as a spinout of DNA2.0, the largest US-based provider of synthetic genes for industrial and academic customers. Calysta leverages extensive expertise in protein engineering, gene synthesis and gene expression optimization to create advanced molecular biology tools able to engineer novel production organisms which enable process technology.

The company’s GPS Bioengineering Platform uses customized algorithms and other advanced tools to quickly convert candidate DNA sequences to testable genes.

• PhyloGPS. The Phylo GPS process enables rapid identification of a starting enzyme to serve as a basis for subsequent protein engineering activities. Researchers using this process to rapidly mine large genome databases for high potential subsets of candidate genes, enabling efficient synthesis and testing.

• GeneGPS. The GeneGPS™ codon optimization methodology allows for efficient and predictable expression of heterologous genes in a target host. This technology is critical for functional testing of mined sequences and building synthetic pathways in industrial host organisms.

• ProteinGPS. The Protein GPS protein engineering system designs proteins with specific, commercially-relevant characteristics. Using key amino acid substitutions, bioinformatics-based mining of available sequence space and advanced machine-learning algorithms, the system obtains significant performance improvements in target protein sequences from sample sizes considerably smaller than those required with conventional directed evolution methods.

• PathwayGPS. The Pathway GPS system builds on other GPS systems to create functionally improved genetic pathways. Using Calysta’s low-cost, high capacity gene synthesis technology, multi-component multi-gene pathways demonstrating optimal industrial-scale performance can be produced with a minimum number of assays.

Alan Shaw, Ph.D, a veteran industrial biotechnology executive, is leading the Calysta team as Chairman, President and CEO, partnered with Josh Silverman, Ph.D., an innovative technology leader with broad experience in biotechnology startup ventures, as Chief Scientific Officer. Dr. Shaw joins Calysta from a decade as President and CEO of Codexis, a developer of cost-advantaged processes for biochemical, biofuel and pharmaceutical production with global customers including Merck, Pfizer, Chemtex and Raizen. Dr. Silverman, who is also co-founder, established and led R&D partnerships and product development collaborations for five biotechnology companies, including Avidia through acquisition by Amgen.

Resources

• Ward N, Larsen Ø, Sakwa J, Bruseth L, Khouri H, et al. (2004) Genomic insights into methanotrophy: The complete genome sequence of Methylococcus capsulatus (Bath). PLoS Biol 2(10): e303.