Metabolic engineering of microbial competitive advantage for industrial fermentation processes

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Science  05 Aug 2016:
Vol. 353, Issue 6299, pp. 583-586
DOI: 10.1126/science.aaf6159

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Xenobiotics to the rescue

Contaminating microorganisms can be highly detrimental to the large-scale fermentation of complex low-cost feedstocks, such as sugarcane or dry-milled corn for biofuels or other industrial purposes. The challenge is that foreign organisms have to be inhibited without using antibiotics because of concerns about spreading antibiotic resistance. Shaw et al. engineered bacteria and yeast to use rare compounds as sources of nutrients (see the Perspective by Lennen). Engineering the common biocatalyst Escherichia coli, for example, to consume melamine as a nitrogen source allowed it to outcompete contaminating organisms. Similarly, engineering yeast to use cyanamide for nitrogen or phosphite for phosphorus also improved competitive fitness.

Science, this issue p. 583; see also p. 542


Microbial contamination is an obstacle to widespread production of advanced biofuels and chemicals. Current practices such as process sterilization or antibiotic dosage carry excess costs or encourage the development of antibiotic resistance. We engineered Escherichia coli to assimilate melamine, a xenobiotic compound containing nitrogen. After adaptive laboratory evolution to improve pathway efficiency, the engineered strain rapidly outcompeted a control strain when melamine was supplied as the nitrogen source. We additionally engineered the yeasts Saccharomyces cerevisiae and Yarrowia lipolytica to assimilate nitrogen from cyanamide and phosphorus from potassium phosphite, and they outcompeted contaminating strains in several low-cost feedstocks. Supplying essential growth nutrients through xenobiotic or ecologically rare chemicals provides microbial competitive advantage with minimal external risks, given that engineered biocatalysts only have improved fitness within the customized fermentation environment.

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