Australian Centre for Water
and Environmental Biotechnology

AWMC Seminar Program: The power of Systems biology: a tale of gas fermentation

Dr. Esteban Marcellin (UQ fellow & Group Leader, AIBN)

Abstract: Due to the contribution of fossil-based industries to climate change, the world faces an increasing need for sustainable production of fuels and chemicals from renewable feedstocks. Recently, acetogens have attracted great interest as cell factories for converting inexpensive and abundant waste feedstocks (e.g. syngas [CO, H2, CO2], industrial waste gases) into high-value products using gas fermentation. Although acetogens arguably use the first carbon fixation pathway on earth to fix CO2, better understanding of metabolism is needed for their rational metabolic engineering.

We have developed a systems biology platform for advancing the understanding and engineering of acetogen metabolism through building the first quantitive links between carbon, energy, and redox metabolism. We use steady-state autotrophic chemostat cultivation coupled to quantitative gas, transcriptomics, proteomics, and metabolomics analyses to reconstruct Clostridium autoethanogenum metabolism in silico using genome-scale metabolic models. Metabolic modelling led to to the discovery of the growth-boosting effect of arginine together with near-abolishment of acetate exctretion. Our systems-level approach revealed a novel regulatory mechanism that controls carbon distribution to maintain ATP homeostasis during growth on syngas and that eventually leads to the collapse of metabolism. Comparing growth on CO, syngas, and CO+H2 showed that H2 supply strongly reduces substrate loss as CO2 with a proportional increase of flux to ethanol. Modelling accurately predicted growth phenotypes, indicated that methylene-THF-reductase reaction was ferredoxin reducing, and in combination with proteomics that ethanol was synthesised through the acetaldehyde:ferredoxin oxidoreductase (AOR) activity. Lastly, we quantify cellular proteome allocation using absolute quantitative proteomics and determine the prevalence of post-translational regulation of acetogen metabolic fluxes.

Our work serves as a reference dataset to advance the understanding and engineering of arguably the first carbon fixation pathway on Earth through an integrated systems-level analysis of a model acetogen. Our findings potentially benefit the gas fermentation bioprocess by describing an alternative route for supplying cells with energy and quantifying the effects of H2 supplementation.


After completing his B. Chem. Eng in Mexico and after working for a polymer company, Dr Marcellin moved to Australia to obtain his PhD in Bioengineering at the University of Queensland. After completing his PhD in 2010, Dr Marcellin has developed systems Biology platforms for Dow, Dow AgroSciences, Zoetis, Pfizer Animal Healthcare, Lanzatech and Novozymes. Dr Marcellin is currently a group Leader at AIBN and the node leader of the Queensland Node of Metabolomics Australia, an NCRIS funded bioplatform aiming at providing world class systems Biology for Australia.


AWMC hosts a free seminar every Friday at 9am in the AIBN Seminar Room.

Event Details
Date & Time: 
Friday, 22 February 2019
9am - 10am
Venue: AIBN Building 75, Level 1 Seminar Room

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