PANT A , DAS B . Microbiome-based therapeutics: opportunity and challenges [J ] Progress in Molecular Biology and Translational Science , 2022 , 191 ( 1 ): 229 - 262 .

SUEZ J , ELINAV E . The path towards microbiome-based metabolite treatment [J ] . Nature Microbiology , 2017 , 2 : 17075 .

FAN Y , PEDERSEN O . Gut microbiota in human metabolic health and disease [J ] . Nature Reviews Microbiology , 2021 , 19 ( 1 ): 55 - 71 .

KIM D Y , LEE S Y , LEE J Y , et al . Gut microbiome therapy: fecal microbiota transplantation vs live biotherapeutic products [J ] . Gut Microbes , 2024 , 16 ( 1 ): 2412376 .

Early clinical trials with live biotherapeutic products: chemistry, manufacturing, and control information [EB/OL ] . FDA , 2016 [ 2025-06-01 ] . https://www.fda.gov/regulatory-information/search-fda-guidance-documents/early-clinical-trials-live-biotherapeutic-products-chemistry-manufacturing-and-control-information https://www.fda.gov/regulatory-information/search-fda-guidance-documents/early-clinical-trials-live-biotherapeutic-products-chemistry-manufacturing-and-control-information .

ROUANET A , BOLCA S , BRU A , et al . Live biotherapeutic products, a road map for safety assessment [J ] . Frontiers in Medicine , 2020 , 7 : 237 .

BOBER J R , BEISEL C L , NAIR N U . Synthetic biology approaches to engineer probiotics and members of the human microbiota for biomedical applications [J ] . Annual Review of Biomedical Engineering , 2018 , 20 : 277 - 300 .

VAN SPRONSEN F J , BLAU N , HARDING C , et al . Phenylketonuria [J ] . Nature Reviews Disease Primers , 2021 , 7 : 36 .

DE GROOT M J , HOEKSMA M , BLAU N , et al . Pathogenesis of cognitive dysfunction in phenylketonuria: review of hypotheses [J ] . Molecular Genetics and Metabolism , 2010 , 99 : S86 - S89 .

杨君 , 吴昭英 , 张丽丽 , 等 . 成人苯丙酮尿症 [J ] . 罕少疾病杂志 , 2023 , 30 ( 8 ): 1 - 2, 10 .

YANG J , WU Z Y , ZHANG L L , et al . Adult phenylketonuria [J ] . Journal of Rare and Uncommon Diseases , 2023 , 30 ( 8 ): 1 - 2, 10 .

BILDER D A , NOEL J K , BAKER E R , et al . Systematic review and meta-analysis of neuropsychiatric symptoms and executive functioning in adults with phenylketonuria [J ] . Developmental Neuropsychology , 2016 , 41 ( 4 ): 245 - 260 .

ISABELLA V M , HA B N , CASTILLO M J , et al . Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria [J ] . Nature Biotechnology , 2018 , 36 ( 9 ): 857 - 864 .

ADOLFSEN K J , CALLIHAN I , MONAHAN C E , et al . Improvement of a synthetic live bacterial therapeutic for phenylketonuria with biosensor-enabled enzyme engineering [J ] . Nature Communications , 2021 , 12 : 6215 .

PUURUNEN M K , VOCKLEY J , SEARLE S L , et al . Safety and pharmacodynamics of an engineered E . coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study [J ] . Nature Metabolism , 2021 , 3 ( 8 ): 1125 - 1132 .

VOCKLEY J , SONDHEIMER N , PUURUNEN M , et al . Efficacy and safety of a synthetic biotic for treatment of phenylketonuria: a phase 2 clinical trial [J ] . Nature Metabolism , 2023 , 5 ( 10 ): 1685 - 1690 .

Synlogic announces decision to discontinue synpheny-3 study and provides corporate update [EB/OL ] .( 2024-02-08 ) [ 2025-01-07 ] . https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-decision-discontinue-synpheny-3-study-and https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-decision-discontinue-synpheny-3-study-and .

CBT 102 -A by CommBio therapeutics for phenylketonuria (PKU): likelihood of approval [EB/OL ] . ( 2024-01-23 )[ 2024-12-20 ] . https://www.pharmaceutical-technology.com/data-insights/cbt102-a-commbio-therapeutics-phenylketonuria-pku-likelihood-of-approval/ https://www.pharmaceutical-technology.com/data-insights/cbt102-a-commbio-therapeutics-phenylketonuria-pku-likelihood-of-approval/ .

王立 , 孔繁智 , 王斗 , 等 . 一种重组肠杆菌及其在降解酪氨酸和苯丙氨酸中的应用 : CN116790468B [P ] . 2023-11-17 .

WANG L , KONG F Z , WANG D , et al . A recombinant Escherichia coli and its application in degrading tyrosine and phenylalanine : CN116790468B [P ] . 2023-11-17 .

邹丹阳 , 董雨萌 , 陈晶瑜 . 活体生物药: 生物技术推动的创新药研发前沿 [J ] . 生物工程学报 , 2023 , 39 ( 4 ): 1275 - 1289 .

ZOU D Y , DONG Y M , CHEN J Y . Live bio therapeutic products: the forefront of innovative drug development driven by biotechnology [J ] . Chinese Journal of Biotechnology , 2023 , 39 ( 4 ): 1275 - 1289 .

DU L , ZONG Y , LI H R , et al . Hyperuricemia and its related diseases: mechanisms and advances in therapy [J ] . Signal Transduction and Targeted Therapy , 2024 , 9 : 212 .

SORENSEN L B . Role of the intestinal tract in the elimination of uric acid [J ] . Arthritis & Rheumatism , 1965 , 8 ( 4 ): 694 - 706 .

GLIOZZI M , MALARA N , MUSCOLI S , et al . The treatment of hyperuricemia [J ] . International Journal of Cardiology , 2016 , 213 : 23 - 27 .

ZHAO R , LI Z M , SUN Y Q , et al . Engineered Escherichia coli Nissle 1917 with urate oxidase and an oxygen-recycling system for hyperuricemia treatment [J ] . Gut Microbes , 2022 , 14 ( 1 ): 2070391 .

HE L N , TANG W , HUANG L , et al . Rational design of a genome-based insulated system in Escherichia coli facilitates heterologous uricase expression for hyperuricemia treatment [J ] . Bioengineering & Translational Medicine , 2023 , 8 ( 2 ): e10449 .

TONG Y , WEI Y F , JU Y J , et al . Anaerobic purinolytic enzymes enable dietary purine clearance by engineered gut bacteria [J ] . Cell Chemical Biology , 2023 , 30 ( 9 ): 1104 - 1114.e7 .

ZOU Z P , LI J L , ZHANG Y F , et al . Empowering probiotics with high xanthine transport for effective hyperuricemia management [J ] . Gut Microbes , 2024 , 16 ( 1 ): 2399213 .

WITTING C , LANGMAN C B , ASSIMOS D , et al . Pathophysiology and treatment of enteric hyperoxaluria [J ] . Clinical Journal of the American Society of Nephrology , 2021 , 16 ( 3 ): 487 - 495 .

HIREMATH S , VISWANATHAN P . Oxalobacter formigenes : a new hope as a live biotherapeutic agent in the management of calcium oxalate renal stones [J ] . Anaerobe , 2022 , 75 : 102572 .

LUBKOWICZ D , HORVATH N G , JAMES M J , et al . An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria [J ] . Molecular Systems Biology , 2022 , 18 ( 3 ): e10539 .

HOPPE B , NIAUDET P , SALOMON R , et al . A randomised Phase Ⅰ/Ⅱ trial to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria [J ] . Pediatric Nephrology , 2017 , 32 ( 5 ): 781 - 790 .

KALANTAR-ZADEH K , JAFAR T H , NITSCH D , et al . Chronic kidney disease [J ] . The Lancet , 2021 , 398 ( 10302 ): 786 - 802 .

BRACK Y , SUN C H , YI D , et al . Discovery of novel tyrosine ammonia lyases for the enzymatic synthesis of p -coumaric acid [J ] . ChemBioChem , 2022 , 23 ( 10 ): e202200062 .

LIU Y Q , XU W Z , XU W . Production of trans -cinnamic and p -coumaric acids in engineered E . coli [J ] . Catalysts , 2022 , 12 ( 10 ): 1144 .

LUBKOWICZ D , HAVA D L , LEWIS K , et al . Rational engineering of Escherichia coli Nissle 1917 as live biotherapeutic to degrade uremic toxin precursors [J ] . ACS Synthetic Biology , 2024 , 13 ( 4 ): 1077 - 1084 .

KRAUS J P , JANOŠÍK M , KOŽICH V , et al . Cystathionine β-synthase mutations in homocystinuria [J ] . Human Mutation , 1999 , 13 ( 5 ): 362 - 375 .

KUMAR T , SHARMA G S , SINGH L R . Homocystinuria: therapeutic approach [J ] . Clinica Chimica Acta , 2016 , 458 : 55 - 62 .

PERREAULT M , MEANS J , GERSON E , et al . The live biotherapeutic SYNB1353 decreases plasma methionine via directed degradation in animal models and healthy volunteers [J ] . Cell Host & Microbe ,

Synlogic announces publication of synpheny-1 phase 2 study of synthetic biotic for phenylketonuria in nature metabolism [EB/OL ] .( 2023-09-28 ) [ 2025-01-07 ] . https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-publication-synpheny-1-phase-2-study https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-publication-synpheny-1-phase-2-study .

Synlogic announces publication of preclinical and clinical data for SYNB1353 as a potential treatment for classical homocystinuria [EB/OL ] .( 2024-02-02 ) [ 2025-01-07 ] . https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-publication-preclinical-and-clinical-data https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-publication-preclinical-and-clinical-data .

KURTZ C B , MILLET Y A , PUURUNEN M K , et al . An engineered E . coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans [J ] . Science Translational Medicine , 2019 , 11 ( 475 ): eaau7975 .

Synlogic discontinues development of SYNB1020 to treat hyperammonemia [EB/OL ] . ( 2019-08-20 )[ 2025-01-07 ] . https://investor.synlogictx.com/news-releases/news-release-details/synlogic-discontinues-development-synb1020-treat-hyperammonemia https://investor.synlogictx.com/news-releases/news-release-details/synlogic-discontinues-development-synb1020-treat-hyperammonemia .

Synlogic announces achievement of proof of concept for SYNB 8802 in enteric hyperoxaluria based on urinary oxalate lowering in Phase 1 b study [EB/OL ] .( 2022-12-15 ) [ 2025-01-07 ] . https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-achievement-proof-concept-synb8802-enteric https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-achievement-proof-concept-synb8802-enteric .

Synlogic announces synthetic biotic for gout developed in partnership with Ginkgo Bioworks [EB/OL ] . ( 2022-08-11 )[ 2025-01-07 ] . https://www.prnewswire.com/news-releases/synlogic-announces-synthetic-biotic-for-gout-developed-in-partnership-with-ginkgo-bioworks-301603915.html https://www.prnewswire.com/news-releases/synlogic-announces-synthetic-biotic-for-gout-developed-in-partnership-with-ginkgo-bioworks-301603915.html .

Pipeline [EB/OL ] . [ 2025-01-07 ] . https://www.synlogictx.com/pipeline/ https://www.synlogictx.com/pipeline/ .

Precigen Actobio announces additional positive interim data from Phase 1 b/ 2 a study of AG 019 ActoBiotics TM , a novel therapy designed to address the underlying cause of Type 1 diabetes [EB/OL ] .( 2021-10-01 ) [ 2025-01-07 ] . https://investors.precigen.com/news-releases/news-release-details/precigen-actobio-announces-additional-positive-interim-data/ https://investors.precigen.com/news-releases/news-release-details/precigen-actobio-announces-additional-positive-interim-data/ .

刘彦强 , 左方圆 , 向斌 . 一种用于催化胆固醇硫酸酯合成的工程微生物及其应用 : CN118853719A [P ] . 2024-10-29 .

LIU Y Q , ZUO F Y , XIANG B . An engineering microorganism for catalyzing the synthesis of cholesterol sulfate ester and its application : CN118853719A [P ] . 2024-10-29 .

CHARBONNEAU M R , ISABELLA V M , LI N , et al . Developing a new class of engineered live bacterial therapeutics to treat human diseases [J ] . Nature Communications , 2020 , 11 : 1738 .

BUECHERL L , MYERS C J . Engineering genetic circuits: advancements in genetic design automation tools and standards for synthetic biology [J ] . Current Opinion in Microbiology , 2022 , 68 : 102155 .

THURSBY E , JUGE N . Introduction to the human gut microbiota [J ] . The Biochemical Journal , 2017 , 474 ( 11 ): 1823 - 1836 .

SONNENBORN U . Escherichia coli strain Nissle 1917-from bench to bedside and back: history of a special Escherichia coli strain with probiotic properties [J ] . FEMS Microbiology Letters , 2016 , 363 ( 19 ): fnw212 .

DERIU E , LIU J Z , PEZESHKI M , et al . Probiotic bacteria reduce Salmonella typhimurium intestinal colonization by competing for iron [J ] . Cell Host & Microbe , 2013 , 14 ( 1 ): 26 - 37 .

FÁBREGA M J , RODRÍGUEZ-NOGALES A , GARRIDO-MESA J , et al . Intestinal anti-inflammatory effects of outer membrane vesicles from Escherichia coli Nissle 1917 in DSS-experimental colitis in mice [J ] . Frontiers in Microbiology , 2017 , 8 : 1274 .

REISTER M , HOFFMEIER K , KREZDORN N , et al . Complete genome sequence of the Gram-negative probiotic Escherichia coli strain Nissle 1917 [J ] . Journal of Biotechnology , 2014 , 187 : 106 - 107 .

KAN A , GELFAT I , EMANI S , et al . Plasmid vectors for in vivo selection-free use with the probiotic E. coli Nissle 1917 [J ] . ACS Synthetic Biology , 2021 , 10 ( 1 ): 94 - 106 .

ZAINUDDIN H S , BAI Y F , MANSELL T J . CRISPR-based curing and analysis of metabolic burden of cryptic plasmids in Escherichia coli Nissle 1917 [J ] . Engineering in Life Sciences , 2019 , 19 ( 6 ): 478 - 485 .

ZHOU S Y , ZHAO L L , ZUO W J , et al . Minimizing endogenous cryptic plasmids t o construct antibiotic-free expression systems for Escherichia coli Nissle 1917 [J ] . Synthetic and Systems Biotechnology , 2024 , 9 ( 1 ): 165 - 175 .

YU X L , LIN C S , YU J , et al . Bioengineered Escherichia coli Nissle 1917 for tumour-targeting therapy [J ] . Microbial Biotechnology , 2020 , 13 ( 3 ): 629 - 636 .

SAEZ-LARA M J , GOMEZ-LLORENTE C , PLAZA-DIAZ J , et al . The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: a systematic review of randomized human clinical trials [J ] . BioMed Research International , 2015 , 2015 : 505878 .

LU K , DONG S W , WU X Y , et al . Probiotics in cancer [J ] . Frontiers in Oncology , 2021 , 11 : 638148 .

WANG C , CUI Y H , QU X J . Optimization of electrotransformation (ETF) conditions in lactic acid bacteria (LAB) [J ] . Journal of Microbiological Methods , 2020 , 174 : 105944 .

O’SULLIVAN D J , KLAENHAMMER T R . High- and low-copy-number Lactococcus shuttle cloning vectors with features for clone screening [J ] . Gene , 1993 , 137 ( 2 ): 227 - 231 .

BAO S J , ZHU L B , ZHUANG Q , et al . Distribution dynamics of recombinant Lactobacillus in the gastrointestinal tract of neonatal rats [J ] . PLoS One , 2013 , 8 ( 3 ): e60007 .

WALKER D C , KLAENHAMMER T R . Isolation of a novel IS3 group insertion element and construction of an integration vector for Lactobacillus spp [J ] . Journal of Bacteriology , 1994 , 176 ( 17 ): 5330 - 5340 .

ENYEART P J , CHIRIELEISON S M , DAO M N , et al . Generalized bacterial genome editing using mobile group Ⅱ introns and Cre-lox [J ] . Molecular Systems Biology , 2013 , 9 : 685 .

ZHU D L , ZHAO K , XU H J , et al . Construction of thyA deficient Lactococcus lactis using the Cre-loxP recombination system [J ] . Annals of Microbiology , 2015 , 65 ( 3 ): 1659 - 1665 .

BERLEC A , ŠKRLEC K , KOCJAN J , et al . Single plasmid systems for inducible dual protein expression and for CRISPR-Cas9/CRISPRi gene regulation in lactic acid bacterium Lactococcus lactis [J ] . Scientific Reports , 2018 , 8 : 1009 .

KIELISZEK M , POBIEGA K , PIWOWAREK K , et al . Characteristics of the proteolytic enzymes produced by lactic acid bacteria [J ] . Molecules , 2021 , 26 ( 7 ): 1858 .

KONGO E . Lactic acid bacteria [M ] . Rijeka, Croatia : InTech , 2013 .

ZIELIŃSKA D , KOLOŻYN-KRAJEWSKA D . Food-origin lactic acid bacteria may exhibit probiotic properties: review [J ] . BioMed Research International , 2018 , 2018 ( 1 ): 5063185 .

PINTO A , BARBOSA J , ALBANO H , et al . Screening of bacteriocinogenic lactic acid bacteria and their characterization as potential probiotics [J ] . Microorganisms , 2020 , 8 ( 3 ): 393 .

SOFI M H , WU Y X , TICER T , et al . A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD [J ] . JCI Insight , 2021 , 6 ( 3 ): e136841 .

LUO X S , KONG Q , WANG Y M , et al . Colonization of Clostridium butyricum in rats and its effect on intestinal microbial composition [J ] . Microorganisms , 2021 , 9 ( 8 ): 1573 .

ZHAO X N , YANG J , JU Z J , et al . Clostridium butyricum ameliorates Salmonella enteritis induced inflammation by enhancing and improving immunity of the intestinal epithelial barrier at the intestinal mucosal level [J ] . Frontiers in Microbiology , 2020 , 11 : 299 .

WANG C , LI W B , WANG H Y , et al . Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota [J ] . BMC Microbiology , 2019 , 19 ( 1 ): 246 .

STOEVA M K , GARCIA-SO J , JUSTICE N , et al . Butyrate-producing human gut symbiont, Clostridium butyricum , and its role in health and disease [J ] . Gut Microbes , 2021 , 13 ( 1 ): 1907272 .

LEE S M , DONALDSON G P , MIKULSKI Z , et al . Bacterial colonization factors control specificity and stability of the gut microbiota [J ] . Nature , 2013 , 501 ( 7467 ): 426 - 429 .

LIU C H , CHANG J H , CHANG Y C , et al . Treatment of murine colitis by Saccharomyces boulardii secreting atrial natriuretic peptide [J ] . Journal of Molecular Medicine , 2020 , 98 ( 12 ): 1675 - 1687 .

MA M P , ZHAO Z T , LIANG Q Y , et al . Overexpression of pEGF improved the gut protective function of Clostridium butyricum partly through STAT3 signal pathway [J ] . Applied Microbiology and Biotechnology , 2021 , 105 ( 14 ): 5973 - 5991 .

DURMUSOGLU D , AL’ABRI I S , COLLINS S P , et al . In situ biomanufacturing of small molecules in the mammalian gut by probiotic Saccharomyces boulardii [J ] . ACS Synthetic Biology , 2021 , 10 ( 5 ): 1039 - 1052 .

WANG Y , CHEN W J , HAN Y Y , et al . Neuroprotective effect of engineered Clostridium butyricum -pMTL007-GLP-1 on Parkinson’s disease mice models via promoting mitophagy [J ] . Bioengineering & Translational Medicine , 2023 , 8 ( 3 ): e10505 .

ZHOU D X , LI S J , HU G , et al . Hypoglycemic effect of C . butyricum -pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus [J ] . Gut Microbes , 2025 , 17 ( 1 ): 2447814 .

WANG W Z , PAN L , HE H S , et al . Systematic enginee ring for efficient uric acid-degrading activity in probiotic yeast Saccharomyces boulardii [J ] . ACS Synthetic Biology , 2025 , 14 ( 6 ): 2030 - 2043 .

GROZDANOV L , RAASCH C , SCHULZE J , et al . Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917 [J ] . Journal of Bacteriology , 2004 , 186 ( 16 ): 5432 - 5441 .

BA F , ZHANG Y F , JI X Y , et al . Expanding the toolbox of probiotic Escherichia coli Nissle 1917 for synthetic biology [J ] . Biotechnology Journal , 2024 , 19 ( 1 ): 2300327 .

FANG M D , ZHANG R T , WANG C Y , et al . Engineering probiotic Escherichia coli Nissle 1917 to block transfer of multiple antibiotic resistance genes by exploiting a type Ⅰ CRISPR-Cas system [J ] . Applied and Environmental Microbiology , 2024 , 90 ( 10 ): e00811-24 .

PRAVESCHOTINUNT P , DURAJ-THATTE A M , GELFAT I , et al . Engineered E . coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut [J ] . Nature Communications , 2019 , 10 ( 1 ): 5580 .

DURRER K E , ALLEN M S , HUNT VON HERBING I . Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU [J ] . PLoS One , 2017 , 12 ( 5 ): e0176286 .

DUAN F F , LIU J H , MARCH J C . Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulin-secreting cells for the treatment of diabetes [J ] . Diabetes , 2015 , 64 ( 5 ): 1794 - 1803 .

GOH Y J , BARRANGOU R . Harnessing CRISPR-Cas systems for precision engineering of designer probiotic lactobacilli [J ] . Current Opinion in Biotechnology , 2019 , 56 : 163 - 171 .

MU Y L , ZHANG C X , LI T H , et al . Development and applications of CRISPR/Cas9-based genome editing in Lactobacillus [J ] . International Journal of Molecular Sciences , 2022 , 23 ( 21 ): 12852 .

ZHOU X Q , WANG X L , LUO H Y , et al . Exploiting heterologous and endogenous CRISPR-Cas systems for genome editing in the probiotic Clostridium butyricum [J ] . Biotechnology and Bioengineering , 2021 , 118 ( 7 ): 2448 - 2459 .

PEI Z M , LIU Y F , YI Z , et al . Diversity within the species Clostridium butyricum : pan-genome, phylogeny, prophage, carbohydrate utilization, and antibiotic resistance [J ] . Journal of Applied Microbiology , 2023 , 134 ( 7 ): lxad127 .

DURMUSOGLU D , HALLER D J , AL’ABRI I S , et al . Programm ing probiotics: diet-responsive gene expression and colonization control in engineered S. boulardii [J ] . ACS Synthetic Biology , 2024 , 13 ( 6 ): 1851 - 1865 .

KWAK S , MAHMUD B , DANTAS G . A tunable and expandable transactivation system in probiotic yeast Saccharomyces boulardii [J ] . ACS Synthetic Biology , 2022 , 11 ( 1 ): 508 - 514 .

ZHENG L G , TAN Y , HU Y C , et al . CRISPR/Cas-based genome editing for human gut commensal Bacteroides species [J ] . ACS Synthetic Biology , 2022 , 11 ( 1 ): 464 - 472 .

SLUSARCZYK A L , LIN A , WEISS R . Foundations for the design and implementation of synthetic genetic circuits [J ] . Nature Reviews Genetics , 2012 , 13 ( 6 ): 406 - 420 .

XIA P F , LING H , FOO J L , et al . Synthetic genetic circuits for programmable biological functionalities [J ] . Biotechnology Advances , 2019 , 37 ( 6 ): 107393 .

HASTY J , MCMILLEN D , COLLINS J J . Engineered gene circuits [J ] . Nature , 2002 , 420 ( 6912 ): 224 - 230 .

SPRINZAK D , ELOWITZ M B . Reconstruction of genetic circuits [J ] . Nature , 2005 , 438 ( 7067 ): 443 - 448 .

ZENG W Z , GUO L K , XU S , et al . High-throughput screening technology in industrial biotechnology [J ] . Trends in Biotechnology , 2020 , 38 ( 8 ): 888 - 906 .

ISHIBASHI N , YAMAZAKI S . Probiotics and safety [J ] . The American Journal of Clinical Nutrition , 2001 , 73 ( 2 ): 465s - 470s .

FULLER R . Probiotics in human medicine [J ] . Gut , 1991 , 32 ( 4 ): 439 - 442 .

MA Y F , MANNA A , MOON T S . Advances in engineering genetic circuits for microbial biocontainment [J ] . Current Opinion in Systems Biology , 2023 , 36 : 100483 .

WANG F Z , ZHANG W W . Synthetic biology: recent progress, biosafety and biosecurity concerns, and possible solutions [J ] . Journal of Biosafety and Biosecurity , 2019 , 1 ( 1 ): 22 - 30 .

ROTTINGHAUS A G , FERREIRO A , FISHBEIN S R S , et al . Genetically stable CRISPR-based kill switches for engineered microbes [J ] . Nature Communications , 2022 , 13 : 672 .

KARBALAEI-HEIDARI H R , BUDISA N . Advanced and safe synthetic microbial chassis with orthogonal translation system integration [J ] . ACS Synthetic Biology , 2024 , 13 ( 9 ): 2992 - 3002 .

SHAO J W , XUE S , YU G L , et al . Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice [J ] . Science Translational Medicine , 2017 , 9 ( 387 ): eaal2298 .

KRAWCZYK K , XUE S , BUCHMANN P , et al . Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice [J ] . Science , 2020 , 368 ( 6494 ): 993 - 1001 .

CHENG A G , HO P Y , ARANDA-DÍAZ A , et al . Design, construction, and in vivo augmentation of a complex gut microbiome [J ] . Cell , 2022 , 185 ( 19 ): 3617 - 3636.e19 .