by Tony Fitzpatrick, Washington University

Synechocystis 6803, image: courtesy ASU

Synechocystis 6803, image: courtesy ASU

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ynechocystis 6803 – a versatile, specialized cyanobacterium – can produce ethanol, hydrogen, butanol, isobutanol and potentially biodiesel. And it’s a natural at converting CO2 to useful chemicals that could help both tame global warming and sustain our energy supply. Genetically engineered, Synechocystis 6803 also has the potential to make commodity chemicals and pharmaceuticals.

Because of its versatility and potential, this microscopic organism is one of the most studied of its kind since it was discovered in 1968, though with such great expectations Synechocystis 6803 has yet to deliver more than small lab-level quantities of anything.

“My goal is to engineer microbes and turn them into microfactories that produce useful chemicals,” Fuzhong Zhang says.

“My goal is to engineer microbes and turn them into microfactories that produce useful chemicals,” Fuzhong Zhang says.

Fuzhong Zhang, PhD, assistant professor of energy, environmental & chemical engineering at Washington University in St. Louis, MO, works with Synechocystis 6803 — as well as other microbes and systems — in the areas of synthetic biology, protein engineering and metabolic engineering, with special focus on synthetic control systems to make the organism reach its untapped prowess.

Zhang says the biotech world has to overcome several challenges to put the engineered microbes in the applications stage. “My goal is to engineer microbes and turn them into microfactories that produce useful chemicals,” Zhang says. “Synechocystis is particularly interesting because it can use CO2 as the only carbon source. Engineering this bacterium would turn the fixed CO2 into metabolites that can be further converted to fuels and other chemicals through designed biosynthetic pathways.

Traditional chemical production requires high pressure and temperatures and lots of chemical solvents, but the microbial approach is very eco-friendly: Once the engineered cyanobacteria start to grow, all they need are water, basic salts and the CO2.

In an academic “scouting report” of Synechocystis, published in the August 2013 Marine Drugs, Zhang and colleagues summarize recent research and conclude that production speed has to be increased and new genetic tools must be developed to control the biochemistry inside Synechocystis so that chemical productivities will be improved to make this technology economically viable.

Zhang says the research community needs better tools to control gene expression. For example, promoters — little stretches of DNA before genes of interest that help control gene expression — with predictable strength are needed. They also need better cellular biosensors that can sense key metabolites and control the production of vital proteins that create the desired chemicals.

And they need to engineer the organisms’ circadian rhythms (day/night) to someday produce organisms that work around the clock making a fuel or chemical. Natural Synechocystis 6803, for instance, produces and stores energy molecules during the day through photosynthesis, but at night, it uses a different set of metabolisms to consume the stored energy. The natural circadian rhythm has to be rewired to make a biofuel 24 hours a day.

“I’m confident that in two or three years we will have more potent tools to engineer gene expression levels and timing, which will speed up the process more accurately and efficiently,” Zhang says.

Funding for this research was provided by the National Science Foundation.

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