Microbial Proteins, at Scale, to Curb Deforestation, CO2 Emissions: Codon Index #48
Plus: The plant-made COVID vaccine is effective at preventing disease.
Hello. Thanks for reading Codon.
TL;DR: Swapping out beef with microbial proteins can massively cut global methane and CO2 emissions. A paper, based on an iGEM project at Imperial College London, uses electricity to control gene circuits in living cells. And a phase 3 clinical trial shows that plant-made vaccines are highly effective at preventing serious COVID-19 disease, across several variants.
Food production and related shipping make up about one-third of global anthropogenic emissions. Livestock occupy about 80% of global agricultural land. Beef is particularly bad; it takes a few hundred gallons of water to produce 1 pound of cow meat.
There are three main ways to replace beef:
Make burgers from plants, especially soybeans.
Use cultured meat, i.e. animal cells grown in a lab.
Make microbial proteins from fermentation.
The third is particularly exciting because fermentation can be scaled massively, one hopes, and fermentation can be tuned with exquisite precision to create new proteins or blends with different tastes and textures.
A new paper in Nature shows that, if the world replaced just 20% of ruminant meat (cows, buffalo, other mammals) with microbial proteins, the demand for ruminant meat would level out completely by 2030; there’d be no surge in demand past that point. If 20% of global meat was made from microbial protein, carbon dioxide emissions by 2050 could be curbed 56% relative to predicted emissions in that year should no changes be made.
The new study also assessed what I would call “pipedream-level” scenarios, like those cases in which 50 or 80% of ruminant proteins were swapped with microbial versions. The global effects from such a change would be even more dramatic (see the figure above; up to a 40% reduction in methane emissions).
Read more at Nature.
Journalists and researchers like to compare engineered cells, imbued with genetic circuits, to electronic circuits. I’ve never agreed with the comparison, even though I’m likely guilty of using it. Cells are inherently noisy and unpredictable. Their insides are a sea of chaotic motion. Electronic circuits behave predictably, reliably. They switch on nearly instantly and turn off with the same rapidity.
Cells are often programmed to do X function by adding Y chemical. This basic approach requires that chemicals diffuse into the cell, bind to a protein, and then that protein does something at the level of DNA. This is really slow. Optogenetics (based on light-responsive proteins) are far faster; there’s also exciting efforts to switch on circuits with ultrasound (pressure waves) and magnets.
Way back in 2018 or so, when I was at Imperial College London, the iGEM team there was trying to build genetic circuits, in living cells, that could be switched on with pulses of electricity. Now they’ve done it.
The key breakthrough came when they tuned the soxS promoter so that its transcription factor — SoxR — recognized one version of the promoter when in its oxidized state, and another promoter in its reduced state. The team tuned these promoters so that they’d exert varying degrees of gene expression. When tested in real cells (including the quick-growing Vibrio natriegens), a +600 mV potential caused gene expression, as measured by GFP fluorescence, to shoot up 11.2-fold.
Read more at Science Advances.
Results are out for a COVID-19 vaccine manufactured in plant cells (tobacco relatives).
In the intention-to-treat group (a comparison of the treatment vs. placebo participants, as originally allocated after randomization), the vaccine was 69.5% effective overall. It was 78.8% effective at preventing moderate-to-severe disease. Out of 165 cases of COVID-19, 40 occurred in the vaccine group. There were no COVID-related deaths. These data are based on 24,141 randomized participants, with a median age of 29 years, and are for any symptomatic infection, which means it’s an aggregate value for a range of variants.
Virus-like particles, extracted from these plant cells, are also “stable for at least 6 months at 2 to 8°C.” That’s a remarkably long time, and vaccines that remain stable long-term in refrigerators are still needed.
Read more at The New England Journal of Medicine.
(↑ = recommended article, * = open access, † = review article, )
*Ultradeep characterisation of translational sequence determinants refutes rare-codon hypothesis and unveils quadruplet base pairing of initiator tRNA and transcript. Höllerer S & Jeschek M. bioRxiv (preprint). Link
↑*Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure. Bohnsack JPW…Pandey SC. Science Advances. Link
*Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution. Yang D…Weissman JS. Cell. Link
*A systems approach discovers the role and characteristics of seven LysR type transcription factors in Escherichia coli. Rodionova IA…Palsson BO. Scientific Reports. Link
*Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multi-omics integration. Kellman BP…Lewis NE. Nature Communications. Link
↑Localized electrical stimulation triggers cell-type-specific proliferation in biofilms. Comerci CJ…Süel GM. Cell Systems. Link
↑Multistep enzyme cascades as a route towards green and sustainable pharmaceutical syntheses. Benítez-Mateos AI, Padrosa DR & Paradisi F. Nature Chemistry. Link
*Rationally engineering santalene synthase to readjust the component ratio of sandalwood oil. Zha W…Zi J. Nature Communications. Link
†Recycling carbon for sustainable protein production using gas fermentation. Marcellin E…Molitor B. Current Opinion in Biotechnology. Link
Tuning Geraniol Biosynthesis via a Novel Decane-Responsive Promoter in Candida glycerinogenes. Zhao C…Zhuge B. ACS Synthetic Biology. Link
*Efficient and accurate prime editing strategy to correct genetic alterations in hiPSC using single EF-1alpha driven all-in-one plasmids. Weuring WJ…Koeleman BPC. bioRxiv (preprint). Link
†Current status, and the developments of hosts and expression systems for the production of recombinant human cytokines. Das PK, Sahoo A & Dasu VV. Biotechnology Advances. Link
Genome Engineering of the Fast-Growing Mycoplasma feriruminatoris toward a Live Vaccine Chassis. Talenton V…Lartigue C. ACS Synthetic Biology. Link
Computational Tools & Models
DeepTESR: A Deep Learning Framework to Predict the Degree of Translational Elongation Short Ramp for Gene Expression Control. Kim DJ…Woo HM. ACS Synthetic Biology. Link
*LOICA: Integrating Models with Data for Genetic Network Design Automation. Vidal G, Vidal-Céspedes C & Rudge TJ. ACS Synthetic Biology. Link
CRISPR & Genetic Control
*Comparative optimization of combinatorial CRISPR screens. Li R…Sellers WR. Nature Communications. Link
CRISPR-Cas Assisted Shotgun Mutagenesis Method for Evolutionary Genome Engineering. Zhao M…Wei D. ACS Synthetic Biology. Link
*A programmable DNA roadblock system using dCas9 and multivalent target sites. Matozel EK, Parziale S & Price AC. PLOS One. Link
*Efficient and Iterative Retron-Mediated in vivo Recombineering in E. coli. Ellington AJ & Reisch CR. Synthetic Biology. Link
Medicine & Diagnostics
↑*Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates. Milani M…Cantore A. Nature Communications. Link
*Rapid, site-specific labeling of “off-the-shelf” and native serum autoantibodies with T cell–redirecting domains. Zappala F…Ozdemir BA. Science Advances. Link
*Efficacy and Safety of the RBD-Dimer–Based Covid-19 Vaccine ZF2001 in Adults. Dai L…ZF2001 Global Trial Group. The New England Journal of Medicine. Link
Antigen-bearing outer membrane vesicles as tumour vaccines produced in situ by ingested genetically engineered bacteria. Yue Y…Nie G. Nature Biomedical Engineering. Link
†Control of host PTMs by intracellular bacteria: An opportunity toward novel anti-infective agents. Stévenin V & Neefjes J. Cell Chemical Biology. Link
*Evaluating and mitigating clinical samples matrix effects on TX-TL cell-free performance. Voyvodic PL…Bonnet J. bioRxiv (preprint). Link
In vivo cyclic induction of the FOXM1 transcription factor delays natural and progeroid aging phenotypes and extends healthspan. Ribeiro R…Logarinho E. Nature Aging. Link
A bivalent Epstein-Barr virus vaccine induces neutralizing antibodies that block infection and confer immunity in humanized mice. Wei C…Nabel GJ. Science Translational Medicine. Link
*Adenovirus type 5 SARS-CoV-2 vaccines delivered orally or intranasally reduced disease severity and transmission in a hamster model. Langel SN…Tucker SN. Science Translational Medicine. Link
*Highly active CAR T cells that bind to a juxtamembrane region of mesothelin and are not blocked by shed mesothelin. Liu X…Pastan I. PNAS. Link
*Custom-made design of metabolite composition in N. benthamiana leaves using CRISPR activators. Selma S…Orzaez D. Plant Biotechnology Journal. Link
Protein & Molecular Engineering
*Novel fold of rotavirus glycan-binding domain predicted by AlphaFold2 and determined by X-ray crystallography. Hu L…Prasad BVV. Communications Biology. Link
*Nanobody assemblies with fully flexible topology enabled by genetically encoded tetrazine amino acids. Van Fossen EM…Mehl RA. Science Advances. Link
*Heterogeneity of the GFP fitness landscape and data-driven protein design. Somermeyer LG…Sarkisyan KS. eLife. Link
“Multiagent” Screening Improves Directed Enzyme Evolution by Identifying Epistatic Mutations. Yang T, Ye Z & Lynch MD. ACS Synthetic Biology. Link
Tools & Technology
*Light-dependent modulation of protein localization and function in living bacteria cells. McQuillen R…Xiao J. bioRxiv (preprint). Link
*Synthetic Mechanotransduction Using Engineered SynNotch Receptors. Sloas DC & Ngo JT. bioRxiv (preprint). Link
Cell-type-specific labeling and profiling of glycans in living mice. Fan X…Chen X. Nature Chemical Biology. Link
†Platforms for Optogenetic Stimulation and Feedback Control. Kumar S & Khammash M. Frontiers in Bioengineering and Biotechnology. Link
*A computational toolbox to investigate the metabolic potential and resource allocation in fission yeast. Grigaitis P…van Heerden JH. bioRxiv (preprint). Link
*Comparison of public discussions of gene editing on social media between the United States and China. Ji J…Barnett GA. PLOS One. Link