SynBERC investigator Chris Voigt and a group of graduate students from his lab took a leap forward in the pursuit of chemicals derived not from petroleum but from renewable sources. The chemical target was methyl halides, a chemical precursor to several high-value chemicals, and which the oil industry already knows how to derive gasoline from.

Although methyl halides are produced naturally by some plants and organisms, the very low levels are not amenable to industrial production. To re-engineer the production of methyl halide, the Voigt lab’s strategy hinged on a single methyl halide transferase (MHT) enzyme, which converts S-adenoyl methionine (SAM, a metabolite that is abundant in organisms) to the final methyl halide product. Their strategy for sussing out the transferase was a synthetic metagenomic approach, i.e. a high-throughput part screening using DNA synthesis. They took a known methyl halide transferase, blasted it against Genbank, and found all the homologs (some with as little as 18% sequence identity). They then chemically synthesized all 89 putative MHT genes from plants, fungi, bacteria, and unidentified organisms present in the NCBI sequence database. They screened them for function, and the best candidate was engineered in Saccharomyces to achieve 190 mg/L-h from glucose to sucrose. To top it off, the Voigt lab created a symbiotic co-culture of their engineered yeast and the cellulolytic bacterium Actinotalea fermentans. The result: Methyl halide production from unprocessed switchgrass, corn stover, sugar cane, and poplar. "If this process were scaled up, we could potentially supplement or replace our dependence on non-renewable petroleum-based fuels and do so in an environmentally responsible way," explains Voigt, who estimates that a pilot plant could be ready for construction in about three years.

Voigt et al. Synthesis of methyl halides from biomass using engineered microbes. J Am Chem Soc. 2009 May 13;131(18):6508-15.