Comparative functional genomics identifies an iron-limited bottleneck in a Saccharomyces cerevisiae strain with a cytosolic-localized isobutanol pathway

Geleynse, 2018, The alcohol-to-jet conversion pathway for drop-in biofuels: techno-economic evaluation, ChemSusChem, 11, 3728, 10.1002/cssc.201801690 Fu, 2021, Recent advances on bio-based isobutanol separation, Energy Convers Manag X, 10, 100059 Gambacorta, 2020, Rewiring yeast metabolism to synthesize products beyond ethanol, Curr Opin Chem Biol, 59, 182, 10.1016/j.cbpa.2020.08.005 Wess, 2019, Improving isobutanol production with the yeast Saccharomyces cerevisiae by successively blocking competing metabolic pathways as well as ethanol and glycerol formation, Biotechnol Biofuels, 12, 1, 10.1186/s13068-019-1486-8 Avalos, 2013, Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols, Nat Biotechnol, 31, 335, 10.1038/nbt.2509 Brat, 2012, Cytosolic re-localization and optimization of valine synthesis and catabolism enables increased isobutanol production with the yeast Saccharomyces cerevisiae, Biotechnol Biofuels, 5, 1, 10.1186/1754-6834-5-65 Shiiba, 2005, Dynamic changes in mitochondrial nucleoids during the transition from anaerobic to aerobic culture in the yeast Saccharomyces cerevisiae, Cytologia, 70, 287, 10.1508/cytologia.70.287 Miyakawa, 2017, Organization and dynamics of yeast mitochondrial nucleoids, Proc Japan Acad Ser B, 93, 339, 10.2183/pjab.93.021 Milne, 2016, Excessive by-product formation: a key contributor to low isobutanol yields of engineered Saccharomyces cerevisiae strains, Metab Eng Commun, 3, 39, 10.1016/j.meteno.2016.01.002 Bastian, 2011, Engineered ketol-acid reductoisomerase and alcohol dehydrogenase enable anaerobic 2-methylpropan-1-ol production at theoretical yield in Escherichia coli, Metab Eng, 13, 345, 10.1016/j.ymben.2011.02.004 Matsuda, 2013, Increased isobutanol production in Saccharomyces cerevisiae by eliminating competing pathways and resolving cofactor imbalance, Microb Cell Factories, 12, 1, 10.1186/1475-2859-12-119 Hammer, 2017, Uncovering the role of branched-chain amino acid transaminases in Saccharomyces cerevisiae isobutanol biosynthesis, Metab Eng, 44, 302, 10.1016/j.ymben.2017.10.001 Ida, 2015, Eliminating the isoleucine biosynthetic pathway to reduce competitive carbon outflow during isobutanol production by Saccharomyces cerevisiae, Microb Cell Factories, 14, 1, 10.1186/s12934-015-0240-6 Park, 2016, Improvement of isobutanol production in Saccharomyces cerevisiae by increasing mitochondrial import of pyruvate through mitochondrial pyruvate carrier, Appl Microbiol Biotechnol, 100, 7591, 10.1007/s00253-016-7636-z Park, 2019, Development of an efficient cytosolic isobutanol production pathway in Saccharomyces cerevisiae by optimizing copy numbers and expression of the pathway genes based on the toxic effect of α-acetolactate, Sci Rep, 9, 1 Zhao, 2018, Optogenetic regulation of engineered cellular metabolism for microbial chemical production, Nature, 555, 683, 10.1038/nature26141 Lane, 2019, Xylose assimilation enhances production of isobutanol in engineered Saccharomyces cerevisiae, Biotechnol Bioeng, 117, 1 Zhang, 2019, Xylose utilization stimulates mitochondrial production of isobutanol and 2-methyl-1-butanol in Saccharomyces cerevisiae, Biotechnol Biofuels, 12, 1, 10.1186/s13068-019-1560-2 Tan, 2016, Controlling central carbon metabolism for improved pathway yields in Saccharomyces cerevisiae, ACS Synth Biol, 5, 116, 10.1021/acssynbio.5b00164 Feng, 2017, Improving isobutanol titers in Saccharomyces cerevisiae with over-expressing NADPH-specific glucose-6-phosphate dehydrogenase (Zwf1), Ann Microbiol, 67, 785, 10.1007/s13213-017-1304-0 Chen, 2011, Increased isobutanol production in Saccharomyces cerevisiae by overexpression of genes in valine metabolism, Biotechnol Biofuels, 4, 1, 10.1186/1754-6834-4-21 Bardone, 2014, Auxotrophic Saccharomyces cerevisiae CEN.PK strains as new performers in ethanol production, Chem Eng Trans, 38, 463 Schiestl, 1989, High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier, Curr Genet, 16, 339, 10.1007/BF00340712 McIlwain, 2016, Genome sequence and analysis of a stress-tolerant, wild-derived strain of Saccharomyces cerevisiae used in biofuels research, G3 Genes, Genomes, Genet, 6, 1757, 10.1534/g3.116.029389 Liu, 2012, Structure-guided engineering of Lactococcus lactis alcohol dehydrogenase LlAdhA for improved conversion of isobutyraldehyde to isobutanol, J Biotechnol, 164, 188, 10.1016/j.jbiotec.2012.08.008 Christianson, 1992, Multifunctional yeast high-copy-number shuttle vectors, Gene, 110, 119, 10.1016/0378-1119(92)90454-W Voth, 2001, Yeast vectors for integration at the HO locus, Nucleic Acids Res, 29, e59, 10.1093/nar/29.12.e59 Gueldener, 2002, A second set of loxP marker cassettes for Cre-mediated multiple gene knockouts in budding yeast, Nucleic Acids Res, 30, e23, 10.1093/nar/30.6.e23 Stoneman, 2020, CRISpy-pop: a web tool for designing CRISPR/Cas9-driven genetic modifications in diverse populations, G3 Genes, Genomes, Genet, 10, 4287, 10.1534/g3.120.401498 Higgins, 2018, Natural variation in the multidrug efflux pump SGE1 underlies ionic liquid tolerance in yeast, Genetics, 210, 219, 10.1534/genetics.118.301161 Ghosh, 2018, OptSSeq explores enzyme expression and function landscapes to maximize isobutanol production rate, Metab Eng, 52, 324, 10.1016/j.ymben.2018.12.008 Güldener, 1996, A new efficient gene disruption cassette for repeated use in budding yeast, Nucleic Acids Res, 24, 2519, 10.1093/nar/24.13.2519 Jacobson, 2020, In vivo thermodynamic analysis of glycolysis in Clostridium thermocellum and thermoanaerobacterium saccharolyticum using 13 C and 2 H tracers, mSystems, 5, 10.1128/mSystems.00736-19 Jacobson, 2019, 2 H and 13 C metabolic flux analysis elucidates in vivo thermodynamics of the ED pathway in Zymomonas mobilis, Metab Eng, 54, 301, 10.1016/j.ymben.2019.05.006 Melamud, 2010, Metabolomic analysis and visualization engine for LC−MS data, Anal Chem, 82, 9818, 10.1021/ac1021166 Clasquin, 2012, LC-MS data processing with MAVEN: a metabolomic analysis and visualization engine, Curr Protoc Bioinf., 37, 10.1002/0471250953.bi1411s37 Gasch, 2002, vol. 350 Bolger, 2014, Trimmomatic: a flexible trimmer for Illumina sequence data, Bioinformatics, 30, 2114, 10.1093/bioinformatics/btu170 Langmead, 2010, vol. 11 Anders, 2015, HTSeq—a Python framework to work with high-throughput sequencing data, Bioinformatics, 31, 166, 10.1093/bioinformatics/btu638 Robinson, 2010, edgeR: a Bioconductor package for differential expression analysis of digital gene expression data, Bioinformatics, 26, 139, 10.1093/bioinformatics/btp616 Benjamini, 1995, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J Roy Stat Soc, 57, 289 de Hoon, 2004, Open source clustering software, Bioinformatics, 20, 1453, 10.1093/bioinformatics/bth078 Saldanha, 2004, Java Treeview—extensible visualization of microarray data, Bioinformatics, 20, 3246, 10.1093/bioinformatics/bth349 Simillion, 2017, Avoiding the pitfalls of gene set enrichment analysis with SetRank, BMC Bioinf, 18, 1, 10.1186/s12859-017-1571-6 Shishkova, 2018, Ultra-high pressure (>30,000 psi) packing of capillary columns enhancing depth of shotgun proteomic analyses, Anal Chem, 90, 11503, 10.1021/acs.analchem.8b02766 Cox, 2008, MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification, Nat Biotechnol, 26, 1367, 10.1038/nbt.1511 Robinson, 2002, FunSpec: a web-based cluster interpreter for yeast, BMC Bioinf, 3, 1, 10.1186/1471-2105-3-35 Lazar, 2009, Polymorphisms in multiple genes contribute to the spontaneous mitochondrial genome instability of Saccharomyces cerevisiae S288C strains, Genetics, 183, 365, 10.1534/genetics.109.104497 Fred, 2002, Getting started with yeast, Methods Enzymol, 350, 3, 10.1016/S0076-6879(02)50954-X Lee, 2015, A highly characterized yeast toolkit for modular, multipart assembly, ACS Synth Biol, 4, 975, 10.1021/sb500366v Sun, 2012, Cloning and characterization of a panel of constitutive promoters for applications in pathway engineering in Saccharomyces cerevisiae, Biotechnol Bioeng, 109, 2082, 10.1002/bit.24481 Martínez-Pastor, 2017, Mechanisms of iron sensing and regulation in the yeast Saccharomyces cerevisiae, World J Microbiol Biotechnol, 33, 1, 10.1007/s11274-017-2215-8 Ljungdahl, 2012, vol. 190 Bamba, 2019, Production of 1,2,4-butanetriol from xylose by Saccharomyces cerevisiae through Fe metabolic engineering, Metab Eng, 56, 17, 10.1016/j.ymben.2019.08.012 Salusjärvi, 2017, Production of ethylene glycol or glycolic acid from D-xylose in Saccharomyces cerevisiae, Appl Microbiol Biotechnol, 101, 8151, 10.1007/s00253-017-8547-3 Yamaguchi-Iwai, 1995, AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae, EMBO J, 14, 1231, 10.1002/j.1460-2075.1995.tb07106.x Benisch, 2014, The bacterial Entner-Doudoroff pathway does not replace glycolysis in Saccharomyces cerevisiae due to the lack of activity of iron-sulfur cluster enzyme 6-phosphogluconate dehydratase, J Biotechnol, 171, 45, 10.1016/j.jbiotec.2013.11.025 Edgar, 2002, Gene Expression Omnibus: NCBI gene expression and hybridization array data repository, Nucleic Acids Res, 30, 207, 10.1093/nar/30.1.207