After more than two decades of intensive molecular genetic research, S. cerevisiae remains the ethanologen of choice. Although industrial strains are genetically largely undefined, it is easily demonstrated that laboratory strains can function perfectly adequately for ethanol production, even for the complex process of manufacturing potable spirits with defined requirements for sensory parameters in the finished prod­uct such as volatiles, higher alcohols, and glycerol content.273 Nevertheless, it is more likely that applying the knowledge gained to the genomic improvement of hardy industrial Saccharomyces (or other Crabtree-positive yeast) strains with proven track records of fermenting very concentrated media to high volumetric yields of ethanol would generate highly suitable biocatalysts for the demanding tasks of growing and metabolizing sugars and oligosaccharides in lignocellulosic hydrolysates.

Even better would be the importing of a methodology developed in the world of industrial biotechnology, that is, “genome breeding,” as outlined by Kyowa Hakko Kogyo,[30] Tokyo, Japan. By comparing the whole genome sequence from the wild — type Corynebacterium glutamicum, the major producing organism for L-lysine and L-glutamate, with gene sequence from an evolved highly productive strain, it was possible to identify multiple changes; with these data, transforming a “clean” wild type to a hyperproducer of lysine was accomplished with only three specific and known mutations in the biosynthetic genes.274 This minimal mutation strain had dis­tinct productivity advantages over the industrial strains that had been developed by chance mutation over decades — a reflection of how many unwanted changes may (and did) occur over prolonged periods of random mutagenesis and selection in the twentieth century.275 Repeating such an exercise with any of the multitude of com­mercial alcohol-producing Saccharomyces yeasts would rapidly identify specific genomic traits for robustness and high productivity on which to construct pentose­utilizing and other capabilities for bioethanol processes.

A radically different option has been outlined in a patent application at the end of May 2007.276 Work undertaken at the J. Craig Venter Institute, Rockville, Maryland, defined a minimal set of 381 protein-encoding genes from Mycoplasma genitalium, including pathways for carbohydrate metabolism, nucleotide biosynthesis, phospho­lipid biosynthesis, and a cellular set of uptake mechanisms for nutrients, that would suffice to generate a free living organism in a nutritionally rich culture medium. Adding in genes for pathways of ethanol and/or hydrogen formation would result in a biofuels producer with maximum biochemical and biotechnological simplicity. The timeline required for practical application and demonstration of such a synthetic organism is presently unclear, although the research is funded by the DOE, under the genome projects of the Department’s Office of Science, with the target of develop­ing a novel recombinant cyanobacterial system for hydrogen production from water and a cellulosome system for the production of ethanol and/or butanol in suitable clostridial cells.277 The drawbacks to such an approach are that it would be highly dependent on the correct balance of supplied nutrients to the organism (with its lim­ited capabilities), requiring highly precise nutrient feeding mechanisms and a likely protracted optimization of the pathways to rival rates of product formation already attainable with older patented or freely available ethanologens.