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DOE OSTI · 3366671

Can protein expression be ‘solved’?

Baranowski, Catherine [The Align Foundation, Covina, CA (United States)] (ORCID:0000000304078609)·Martin, Hector Garcia [USDOE Agile BioFoundry, Emeryville, CA (United States); Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)] (ORCID:0000000245569685)·Oyarzún, Diego A. [Univ. of Edinburgh, Scotland (United Kingdom)] (ORCID:0000000203815278)·Spinner, Aviv [The Align Foundation, Covina, CA (United States)] (ORCID:0000000198450787)·Desai, Bijoy [The Align Foundation, Covina, CA (United States)] (ORCID:0000000257137855)·Petzold, Christopher J. [USDOE Agile BioFoundry, Emeryville, CA (United States); Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)] (ORCID:0000000282705228)·Nikolados, Evangelos-Marios [Myria Biosciences AG, Basel (Switzerland)] (ORCID:0000000323030889)·Jaaks-Kraatz, Sebastian [Friedrich Miescher Inst. for Biomedical Research (FMI), Basel (Switzerland)] (ORCID:0000000322659052)·Gaber, Aljaž [Univ. of Ljubljana (Slovenia)] (ORCID:0000000237443142)·Chalkley, Robert J. [Univ. of California, San Francisco, CA (United States)] (ORCID:0000000297577302)·Scannell, Devin [Decade, Inc., Mountain View, CA (United States)] (ORCID:0000000281885992)·Sevey, Rachel [The Align Foundation, Covina, CA (United States)]·Jewett, Michael C. [Stanford Univ., CA (United States)] (ORCID:0000000329486211)·Kelly, Peter J. [The Align Foundation, Covina, CA (United States)]·DeBenedictis, Erika A. [The Align Foundation, Covina, CA (United States)] (ORCID:0000000279332651)
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Abstract

Recombinant protein expression is central to biotechnology’s application in academic exploration as well as human health, climate applications and the bioeconomy in general. However, not all proteins can be expressed in all organisms, and the field lacks a predictive model of soluble protein overexpression that could replace laborious experimental trial-and-error. Here, we discuss the state of the field and identify the lack of large, high-fidelity datasets as the primary bottleneck to progress. We review possible assays that could be used for data collection to identify a path toward an extensible experimental platform for collecting soluble recombinant protein overexpression data across organisms. We suggest that the resulting dataset should be used to train increasingly generalizable predictive models of protein expression to answer the question: “How can predictive protein expression be solved?”.

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59 BASIC BIOLOGICAL SCIENCESmachine learningopen datasetspredictive modelsprotein expression

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Baranowski, Catherine [The Align Foundation, Covina, CA (United States)] (ORCID:0000000304078609), Martin, Hector Garcia [USDOE Agile BioFoundry, Emeryville, CA (United States); Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)] (ORCID:0000000245569685), Oyarzún, Diego A. [Univ. of Edinburgh, Scotland (United Kingdom)] (ORCID:0000000203815278), Spinner, Aviv [The Align Foundation, Covina, CA (United States)] (ORCID:0000000198450787), Desai, Bijoy [The Align Foundation, Covina, CA (United States)] (ORCID:0000000257137855), Petzold, Christopher J. [USDOE Agile BioFoundry, Emeryville, CA (United States); Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)] (ORCID:0000000282705228), Nikolados, Evangelos-Marios [Myria Biosciences AG, Basel (Switzerland)] (ORCID:0000000323030889), Jaaks-Kraatz, Sebastian [Friedrich Miescher Inst. for Biomedical Research (FMI), Basel (Switzerland)] (ORCID:0000000322659052), Gaber, Aljaž [Univ. of Ljubljana (Slovenia)] (ORCID:0000000237443142), Chalkley, Robert J. [Univ. of California, San Francisco, CA (United States)] (ORCID:0000000297577302), Scannell, Devin [Decade, Inc., Mountain View, CA (United States)] (ORCID:0000000281885992), Sevey, Rachel [The Align Foundation, Covina, CA (United States)], Jewett, Michael C. [Stanford Univ., CA (United States)] (ORCID:0000000329486211), Kelly, Peter J. [The Align Foundation, Covina, CA (United States)], DeBenedictis, Erika A. [The Align Foundation, Covina, CA (United States)] (ORCID:0000000279332651). 2025-06-02. Can protein expression be ‘solved’?. https://doi.org/10.1016/j.tibtech.2025.04.021

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