{"doi":"10.1016/j.mtbio.2023.100677","title":"Gene expression dynamics in input-responsive engineered living materials programmed for bioproduction","abstract":"Engineered living materials (ELMs) fabricated by encapsulating microbes in hydrogels have great potential as bioreactors for sustained bioproduction. While long-term metabolic activity has been demonstrated in these systems, the capacity and dynamics of gene expression over time is not well understood. Thus, we investigate the long-term gene expression dynamics in microbial ELMs constructed using different microbes and hydrogel matrices. Through direct gene expression measurements of engineered E. coli in F127-bisurethane methacrylate (F127-BUM) hydrogels, we show that inducible, input-responsive genetic programs in ELMs can be activated multiple times and maintained for multiple weeks. Interestingly, the encapsulated bacteria sustain inducible gene expression almost 10 times longer than free-floating, planktonic cells. These ELMs exhibit dynamic responsiveness to repeated induction cycles, with up to 97% of the initial gene expression capacity retained following a subsequent induction event. We demonstrate multi-week bioproduction cycling by implementing inducible CRISPR transcriptional activation (CRISPRa) programs that regulate the expression of enzymes in a pteridine biosynthesis pathway. ELMs fabricated from engineered S. cerevisiae in bovine serum albumin (BSA) - polyethylene glycol diacrylate (PEGDA) hydrogels were programmed to express two different proteins, each under the control of a different chemical inducer. We observed scheduled bioproduction switching between betaxanthin pigment molecules and proteinase A in S. cerevisiae ELMs over the course of 27 days under continuous cultivation. Overall, these results suggest that the capacity for long-term genetic expression may be a general property of microbial ELMs. This work establishes approaches for implementing dynamic, input-responsive genetic programs to tailor ELM functions for a wide range of advanced applications.","journal":"Materials Today Bio","year":2023,"id":333867,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1039205,"name":"Gökçe Altın","orcid":"0000-0001-9577-3257","position":1,"is_corresponding":false},{"id":1061698,"name":"Benjamin I. Tickman","orcid":"0000-0002-3008-6090","position":2,"is_corresponding":false},{"id":902131,"name":"Cholpisit Kiattisewee","orcid":"0000-0002-6351-7352","position":3,"is_corresponding":false},{"id":1040760,"name":"Shuo‐Fu Yuan","orcid":"0000-0002-5530-8702","position":4,"is_corresponding":false},{"id":1040759,"name":"Sierra M. Brooks","orcid":"0000-0002-6914-2504","position":5,"is_corresponding":false},{"id":1061699,"name":"Jitkanya Wong","orcid":"0000-0003-1151-2004","position":6,"is_corresponding":false},{"id":671949,"name":"Hal S. Alper","orcid":"0000-0002-8246-8605","position":7,"is_corresponding":false},{"id":253501,"name":"Alshakim Nelson","orcid":"0000-0001-8060-8611","position":8,"is_corresponding":false},{"id":902132,"name":"James M. Carothers","orcid":"0000-0001-6728-7833","position":9,"is_corresponding":false},{"id":1061697,"name":"Widianti Sugianto","orcid":"0000-0003-4123-6063","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:09:44.297718Z","pmid":"37273790","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}