Organic Sulfur Metabolism Laboratory:
How bacteria get what they need to grow and survive
Just like humans need to eat food for energy and to grow, bacteria need to acquire nutrients from environment they live in. This isn’t always an easy task. Many times a particular element like nitrogen, sulfur, or phosphorous needed to build DNA and proteins is not very plentiful. Other times they are locked away in chemical compounds that make them difficult to access. Out in the ocean, sulfur is plentiful and in an easy to use form, sulfate. But on land and in freshwater environments sulfate isn’t always so abundant. Rather, organic forms of sulfur may be available like methylthioadenosine, dimethyl sulfide or methylthioethanol. We study how bacteria metabolize these compounds to acquire the sulfur they need and what they do with the remaining organic carbon.
Here are some of the highlights of what the North Lab studies
1. Nitrogenase-Like Enzymes that make Ethylene and Methane
Nitrogenase is the bacterial enzyme complex responsible for the reduction of nitrogen gas into biologically available ammonia. About 50% of all biologically available ammonia is made by nitrogenase annually. However, there is a wealth of enzymes related to nitrogenase that have different and in many cases unknown function. Recently, the North lab discovered that a certain group of Nitrogenase-Like proteins surprisingly function in sulfur metabolism. The protein complex, named methylthio-alkane reductase (Mar for short) takes volatile organic sulfur compounds like dimethyl sulfide and methylthio-ethanol, reduces them to liberate the needed sulfur, and in the process releases methane and ethylene. Both of these gases have vital roles in the environment as a potent greenhouse gas and plan signaling hormone, respectively. These findings were recently published in the journal Science. Nitrogenase-like complexes are ripe for study to understand their structure, chemistry, and role in environmental methane and ethylene levels.
2. Metabolic Engineering of Bacteria for Bioproducts
Nearly all plastics made on early begin with fossil fuels. Huge amounts of energy are required to convert shale gas and crude oil components into ethylene and propylene. From there the ethylene and propylene can be made into all manner of plastics. Clearly this intense energy demand and reliance on fossil fuels is not sustainable. Using state of the art metabolic engineering, in collaboration with environmental microbiologists and computational modeling teams, we are mining the wealth of sequenced genomes and screening genes for optimum function and activity in the synthesis of ethylene and other bioproducts.
3. New Sulfur Metabolism Pathways
All organisms need methionine not just for making proteins, but also for making S-adenosyl-L-methionine. This compound serves a myriad of functions from DNA methylation to cell signaling to generation of radicals for enzymes that use a radical mechanism. But after it is used, often there is waste left behind containing precious sulfur. This waste, or 5′-methylthioadenosine (MTA), is inhibitory to cell growth and must either be disposed of or converted back into methionine. As it turns out, bacteria have figured out many ways to do this, employing some novel chemistries and producing some useful byproducts. The newly discovered DHAP shunt, widely found in pathogenic bacteria, metabolizes MTA for carbon and sulfur salvage (below). We are working to decipher the role of this pathway in pathogenic bacteria and to uncover new sulfur salvage pathways with new chemistries and potential applications in human health and renewable bioproducts.
4. RubisCO and RubisCO-Like proteins in Sulfur Metabolism
RubisCO, or ribulose-1,5-bisphosphate carboxylase/oxygenase is the keystone enzyme in which gaseous carbon dioxide gets incorporated into organic carbon. The genes for RubisCO in bacteria are typically associated with genes for the Calvin-Benson-Bassham cycle (carbon fixation) or associated with genes for degrading nucleotides (carbon salvage). A while back, as more and more bacteria began to be sequenced, scientists discovered that like with nitrogenase, there is a wealth of protein sequence similar but distinct from RubisCO. These proteins could not perform CO2 fixation, so what were they doing? Thus was the discovery of the RubisCO-like proteins and soon it became clear many were involved in sulfur salvage. What’s more, it was discovered that RubisCO itself catalyzes a reaction involved in sulfur salvage (left image, dashed arrow). The North lab continues to characterize the function of newly discovered RubisCO-like proteins in sulfur and carbon metabolism and is working to uncover the precise reaction RubisCO performs in sulfur metabolism.