Journal
METABOLIC ENGINEERING
Volume 69, Issue -, Pages 87-97Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2021.11.003
Keywords
Cyanobacteria; Strain design; Genome-scale metabolic model; Isobutanol; 2-methyl-1-butanol; Nitrate assimilation
Categories
Funding
- Office of Science (BER), U.S. Department of Energy [DE-SC0008103]
- NIH NHGRI Genomic Sciences Training Program at UW-Madison [T32 HG002760]
- U.S. Department of Energy (DOE) [DE-SC0008103] Funding Source: U.S. Department of Energy (DOE)
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The study uses a genome-scale metabolic model to predict and design novel cyanobacterial strains for improved production of biofuel alcohols.
Cyanobacteria hold promise for renewable chemical production due to their photosynthetic nature, but engineered strains frequently display poor production characteristics. These difficulties likely arise in part due to the distinctive photoautotrophic metabolism of cyanobacteria. In this work, we apply a genome-scale metabolic model of the cyanobacteria Synechococus sp. PCC 7002 to identify strain designs accounting for this unique metabolism that are predicted to improve the production of various biofuel alcohols (e.g. 2-methyl-1-butanol, isobutanol, and 1-butanol) synthesized via an engineered biosynthesis pathway. Using the model, we identify that the introduction of a large, non-native NADH-demand into PCC 7002's metabolic network is predicted to enhance production of these alcohols by promoting NADH-generating reactions upstream of the production pathways. To test this, we construct strains of PCC 7002 that utilize a heterologous, NADH-dependent nitrite reductase in place of the native, ferredoxin-dependent enzyme to create an NADH-demand in the cells when grown on nitrate-containing media. We find that photosynthetic production of both isobutanol and 2-methyl-1butanol is significantly improved in the engineered strain background relative to that in a wild-type background. We additionally identify that the use of high-nutrient media leads to a substantial prolongment of the production curve in our alcohol production strains. The metabolic engineering strategy identified and tested in this work presents a novel approach to engineer cyanobacterial production strains that takes advantage of a unique aspect of their metabolism and serves as a basis on which to further develop strains with improved production of these alcohols and related products.
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