Exploring eukaryotic formate metabolisms to enhance microbial growth and lipid accumulation.
BACKGROUND
C1 substrates (such as formate and methanol) are promising feedstock for biochemical/biofuel production. Numerous studies have been focusing on engineering heterologous pathways to incorporate C1 substrates into biomass, while the engineered microbial hosts often demonstrate inferior fermentation performance due to substrate toxicity, metabolic burdens from engineered pathways, and poor enzyme activities. Alternatively, exploring native C1 pathways in non-model microbes could be a better solution to address these challenges.


RESULTS
An oleaginous fungus,Umbelopsis isabellina, demonstrates an excellent capability of metabolizing formate to promote growth and lipid accumulation. By co-feeding formate with glucose at a mole ratio of 3.9:1, biomass and lipid productivities of the culture in 7.5 L bioreactors were improved by 20 and 70%, respectively.13C-metabolite analysis, genome annotations, and enzyme assay further discovered that formate not only provides an auxiliary energy source [promoting NAD(P)H and ATP] for cell anabolism, but also contributes carbon backbones via folate-mediated C1 pathways. More interestingly, formate addition can tune fatty acid profile and increase the portion of medium-chain fatty acids, which would benefit conversion of fungal lipids for high-quality biofuel production. Flux balance analysis further indicates that formate co-utilization can power microbial metabolism to improve biosynthesis, particularly on glucose-limited cultures.


CONCLUSIONS
This study demonstratesUmbelopsis isabellina'sstrong capability for co-utilizing formate to produce biomass and enhance fatty acid production. It is a promising non-model platform that can be potentially integrated with photochemical/electrochemical processes to efficiently convert carbon dioxide into biofuels and value-added chemicals.
Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, MI 48824-1323 USA.
Zhiguo
Z
Liu
Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, MO 63110 USA.
Tolutola
T
Oyetunde
Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, MO 63110 USA.
Whitney D
WD
Hollinshead
Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, MI 48824-1323 USA.|Department of Biology, Heinrich Heine University, 40225 Düsseldorf, Germany.
Anna
A
Hermanns
Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, MO 63110 USA.
Yinjie J
YJ
Tang
Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, MI 48824-1323 USA.
Wei
W
Liao
Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, MI 48824-1323 USA.
Yan
Y
Liu
13C; Fatty acids; Flux balance analysis; NAD(P)H; One-carbon metabolic pathway