By Pranali Dalvi
Using microbes to manufacture chemicals is starting to be cheaper and greener than traditional chemistry. And their feedstock is sugar, not oil.
On Friday, Dr. Michael Lynch spoke to an engaged audience about how microbes have ushered in a new era in metabolic and genetic engineering. Lynch is the co-founder and CSO of OPX Biotechnologies, a Colorado-based company that makes bio-based chemicals and fuels from microbes. OPXBIO microbes produce fatty acids from hydrogen and carbon dioxide. In turn, the fatty acids are used to make cleaners, detergents, jet fuel, and diesel.
Lynch said it’s easier to understand the genetic circuits and enzymatic pathways of microbes, thanks to much cheaper DNA sequencing. What we still lack though, is an understanding of how to rationally design complex biological systems – likely because we fail to recognize the interplay among an organism’s genotype, phenotype, and environment.
It’s a complex set of factors that go into making phenotypic traits such as color, size, or shape.
“In an industrial setting [phenotypes] are equivalent to metabolism or higher production of the product of interest,” Lynch said. “In a clinical setting, [phenotypes] could be virulence or pathogenesis.”
One approach to understanding how phenotypes are controlled has been through functional genomics.
Let’s say we take a population of wildtype microorganisms and introduce genetic modifications in a controlled way. Next, we selectively screen for the phenotype of interest and compare the sequence of this phenotype to the wildtype to pinpoint the genetic mutations that made the difference.
Comparing phenotypes one at a time is inefficient, though. Lynch wanted to find a way to speed up this process.
“We wanted a process or technology or toolkit that evaluates all of your genes in parallel in a single experiment for the phenotype of interest,” Lynch explained.
Lynch found his inspiration in microbial biofilms, extracellular polysaccharide matrices that grow quickly.
Lynch’s studies revealed that microbial cultures grown in enriched media made biofilms, while those in minimal media did not. In a process known as destructional mutagenesis, Lynch and his colleagues then knocked out biofilm-making genes to identify what genes cause the biofilm phenotype in enriched medium but prevent it in minimal medium.
Lynch saw the individual microbial systems as factories that he can genetically modify to produce chemical compounds in biofilms – specifically, 3-hydroxypropionic acid – that can be chemically converted to commercially relevant compounds such as acrylic.
Scientists at OPXBIO have cracked the code for making acrylic from sugar. They give sugar feedstocks to genetically modified bacteria, whose enzymes convert the sugar into acrylic molecules. Acrylic has broad commercial applications in paints, adhesives, diapers, detergents, and even fuel – a $10 billion global market.