José L. Avalos

Contact
javalos@princeton.eduResearch Area
Biochemistry, Biophysics & Structural BiologyResearch Focus
Metabolic engineering, organelle engineering, synthetic biology, structural biology, and protein engineeringMetabolic Engineering
Metabolic engineering is the application of genetic engineering to modify and optimize the metabolism and regulatory systems of an organism to produce or degrade a desired compound. We are currently focused on engineering microorganisms (mostly yeasts) for two possible goals: 1) to produce molecules of commercial value, such as biofuels, bioplastics, commodity chemicals, or specialty chemicals (drugs, pigments, flavorants, etc.) from renewable sources, including cellulosic biomass; or 2) to degrade or remove contaminants from the environment (bioremediation).
Organelle Engineering
Subcellular engineering is a fast-growing field in bioengineering, in which metabolic pathways or other synthetic functions are targeted to specific cellular organelles to take advantage of their unique environments, metabolites, and enzymes, as well as their physical separation from the cytosol. We are particularly interested in mitochondrial engineering, where we have shown that targeting metabolic pathways to yeast mitochondria is an effective way to enhance the productivity of engineered pathways. In addition, we are interested in engineering the mitochondrial physiology to enhance metabolic pathways targeted to this highly dynamic, and versatile organelle.
Synthetic Biology
Synthetic biology combines molecular biology, genetic engineering (including genome editing), directed evolution, biophysics, computational biology, and protein engineering, aiming to generate synthetic phenotypes (analogous to synthetic chemistry aiming to generate synthetic molecules by designing series of chemical reactions). We are particularly interested in developing biosensors and regulatory genetic circuits applicable to metabolic engineering. Biosensors are useful to measure, monitor, screen, or select for desired functions (either natural or engineered). Genetic circuits are useful to control engineered metabolisms and other engineered functions in the cell.
Structural Biology and Protein Engineering
Our efforts in synthetic biology and metabolic engineering are complemented by fundamental studies on the molecular structure and function of the proteins involved, such as enzymes, transmembrane transporters, receptors, and transcription factors. To study these proteins in molecular detail, we use different biophysical and biochemical methods, including X-ray crystallography. Understanding the relationship between the structure and function of these proteins significantly enhances our ability to engineer them with new functions relevant to metabolic engineering or synthetic biology.
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Optogenetics Illuminates Applications in Microbial Engineering. Annu Rev Chem Biomol Eng. 2022 ;. .
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Light-Controlled Fermentations for Microbial Chemical and Protein Production. J Vis Exp. 2022 ;(181). .
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Biosensor for branched-chain amino acid metabolism in yeast and applications in isobutanol and isopentanol production. Nat Commun. 2022 ;13(1):270. .
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Physiological limitations and opportunities in microbial metabolic engineering. Nat Rev Microbiol. 2022 ;20(1):35-48. .
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Cellulosic biofuel production using emulsified simultaneous saccharification and fermentation (eSSF) with conventional and thermotolerant yeasts. Biotechnol Biofuels. 2021 ;14(1):157. .
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Lights up on organelles: Optogenetic tools to control subcellular structure and organization. WIREs Mech Dis. 2021 ;13(1):e1500. .
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Engineering acetyl-CoA supply and ERG9 repression to enhance mevalonate production in Saccharomyces cerevisiae. J Ind Microbiol Biotechnol. 2021 ;48(9-10). .
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The Inducible Q System Enables Simultaneous Optogenetic Amplification and Inversion in for Bidirectional Control of Gene Expression. ACS Synth Biol. 2021 ;10(8):2060-2075. .
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Optogenetic Control of Microbial Consortia Populations for Chemical Production. ACS Synth Biol. 2021 ;10(8):2015-2029. .
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Optogenetic Amplification Circuits for Light-Induced Metabolic Control. ACS Synth Biol. 2021 ;10(5):1143-1154. .
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Dynamical Modeling of Optogenetic Circuits in Yeast for Metabolic Engineering Applications. ACS Synth Biol. 2021 ;10(2):219-227. .
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Optogenetic control of the lac operon for bacterial chemical and protein production. Nat Chem Biol. 2021 ;17(1):71-79. .
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Design and Characterization of Rapid Optogenetic Circuits for Dynamic Control in Yeast Metabolic Engineering. ACS Synth Biol. 2020 ;9(12):3254-3266. .
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Optogenetics and biosensors set the stage for metabolic cybergenetics. Curr Opin Biotechnol. 2020 ;65:296-309. .
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¡Viva la mitochondria!: harnessing yeast mitochondria for chemical production. FEMS Yeast Res. 2020 ;20(6). .
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Optogenetic control of protein binding using light-switchable nanobodies. Nat Commun. 2020 ;11(1):4044. .
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Development of light-responsive protein binding in the monobody non-immunoglobulin scaffold. Nat Commun. 2020 ;11(1):4045. .
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Developmental plasticity shapes social traits and selection in a facultatively eusocial bee. Proc Natl Acad Sci U S A. 2020 ;117(24):13615-13625. .
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The skin microbiome of elasmobranchs follows phylosymbiosis, but in teleost fishes, the microbiomes converge. Microbiome. 2020 ;8(1):93. .
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Mitochondrial Compartmentalization Confers Specificity to the 2-Ketoacid Recursive Pathway: Increasing Isopentanol Production in . ACS Synth Biol. 2020 ;9(3):546-555. .
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Xylose assimilation enhances the production of isobutanol in engineered Saccharomyces cerevisiae. Biotechnol Bioeng. 2020 ;117(2):372-381. .
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Critical Roles of the Pentose Phosphate Pathway and GLN3 in Isobutanol-Specific Tolerance in Yeast. Cell Syst. 2019 ;9(6):534-547.e5. .
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Light-based control of metabolic flux through assembly of synthetic organelles. Nat Chem Biol. 2019 ;15(6):589-597. .
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SEIS: Insight's Seismic Experiment for Internal Structure of Mars. Space Sci Rev. 2019 ;215(1):12. .
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Xylose utilization stimulates mitochondrial production of isobutanol and 2-methyl-1-butanol in . Biotechnol Biofuels. 2019 ;12:223. .
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Metabolic pathway engineering. Synth Syst Biotechnol. 2018 ;3(1):1-2. .
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Mapping Local and Global Liquid Phase Behavior in Living Cells Using Photo-Oligomerizable Seeds. Cell. 2018 ;175(6):1467-1480.e13. .
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Current and future modalities of dynamic control in metabolic engineering. Curr Opin Biotechnol. 2018 ;52:56-65. .
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Optogenetic regulation of engineered cellular metabolism for microbial chemical production. Nature. 2018 ;555(7698):683-687. .
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Harnessing yeast organelles for metabolic engineering. Nat Chem Biol. 2017 ;13(8):823-832. .
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Uncovering the role of branched-chain amino acid transaminases in Saccharomyces cerevisiae isobutanol biosynthesis. Metab Eng. 2017 ;44:302-312. .
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Traditional and novel tools to probe the mitochondrial metabolism in health and disease. Wiley Interdiscip Rev Syst Biol Med. 2017 ;9(2). .
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Metabolic engineering: Biosensors get the green light. Nat Chem Biol. 2016 ;12(11):894-895. .
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Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols. Nat Biotechnol. 2013 ;31(4):335-41. .
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Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution. Science. 2009 ;326(5960):1668-74. .
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The structural basis of sirtuin substrate affinity. Biochemistry. 2006 ;45(24):7511-21. .
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Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide. Structure. 2006 ;14(8):1231-40. .
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Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme. Mol Cell. 2005 ;17(6):855-68. .