Background: Serotonin (5-hydroxytryptamine, 5-HT) is a pivotal neurotransmitter with broad clinical relevance. However, its industrial-scale microbial production remains a significant challenge. In this study, we engineered Streptomyces albulus to develop an efficient enzymatic cascade for the scalable and high-yield biosynthesis of 5-HT.
Results: To enhance 5-HT production, we first overexpressed the native 5-hydroxytryptophan decarboxylase (5-OHTDC) in S. albulus, which strengthened the final decarboxylation step. Using 5-hydroxytryptophan as the substrate, this modification achieved a 5-HT titer of 6.87 g/L. We then introduced Escherichia coli L-tryptophan permease (Mtr) to improve cellular uptake of L-tryptophan, along with Actinomadura luzonensis tryptophan 5-hydroxylase (Luz15) to catalyze the hydroxylation of L-tryptophan. This triple-enzyme expression system (5-OHTDC/Mtr/Luz15) enabled the direct conversion of L-tryptophan to 5-HT, yielding 3.46 g/L. Leveraging the innate L-tryptophan biosynthesis capability of S. albulus, we pursued direct fermentative production from low-cost carbon sources. Mannitol was identified as the optimal substrate, supporting a maximum 5-HT titer of 6.54 g/L in fed-batch fermentation. Finally, implementing an L-tryptophan feeding strategy further boosted the final 5-HT titer to 12.0 g/L.
Conclusions: This work establishes S. albulus as an efficient microbial platform for high-level 5-HT production. The engineered strain and optimized fermentation process demonstrate strong potential for industrial application and provide a versatile chassis for synthesizing diverse tryptophan-derived bioactive compounds.
{"title":"Metabolic engineering of Streptomyces albulus for de novo serotonin production.","authors":"Yuan Zhang, Aoxiang Liu, Min Zhang, Jiabei Song, Qian Wang, Yongxuan Liu, Qingshou Yao, Linghui Kong, Xiuwen Wang, Jiayang Qin","doi":"10.1186/s12934-026-02995-y","DOIUrl":"10.1186/s12934-026-02995-y","url":null,"abstract":"<p><strong>Background: </strong>Serotonin (5-hydroxytryptamine, 5-HT) is a pivotal neurotransmitter with broad clinical relevance. However, its industrial-scale microbial production remains a significant challenge. In this study, we engineered Streptomyces albulus to develop an efficient enzymatic cascade for the scalable and high-yield biosynthesis of 5-HT.</p><p><strong>Results: </strong>To enhance 5-HT production, we first overexpressed the native 5-hydroxytryptophan decarboxylase (5-OHTDC) in S. albulus, which strengthened the final decarboxylation step. Using 5-hydroxytryptophan as the substrate, this modification achieved a 5-HT titer of 6.87 g/L. We then introduced Escherichia coli L-tryptophan permease (Mtr) to improve cellular uptake of L-tryptophan, along with Actinomadura luzonensis tryptophan 5-hydroxylase (Luz15) to catalyze the hydroxylation of L-tryptophan. This triple-enzyme expression system (5-OHTDC/Mtr/Luz15) enabled the direct conversion of L-tryptophan to 5-HT, yielding 3.46 g/L. Leveraging the innate L-tryptophan biosynthesis capability of S. albulus, we pursued direct fermentative production from low-cost carbon sources. Mannitol was identified as the optimal substrate, supporting a maximum 5-HT titer of 6.54 g/L in fed-batch fermentation. Finally, implementing an L-tryptophan feeding strategy further boosted the final 5-HT titer to 12.0 g/L.</p><p><strong>Conclusions: </strong>This work establishes S. albulus as an efficient microbial platform for high-level 5-HT production. The engineered strain and optimized fermentation process demonstrate strong potential for industrial application and provide a versatile chassis for synthesizing diverse tryptophan-derived bioactive compounds.</p>","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-24DOI: 10.1186/s12934-026-02972-5
Noura Salah Nour, Sawsan Abd Ellatif, El-Sayed Mahdy, Ahmed Atef El-Beih, Hatem El-Mezayen
{"title":"Statistical optimization of Chlorella vulgaris polysaccharides-mediated synthesis of platinum nanoparticles with dual functions: anticancer and anticoagulant activities.","authors":"Noura Salah Nour, Sawsan Abd Ellatif, El-Sayed Mahdy, Ahmed Atef El-Beih, Hatem El-Mezayen","doi":"10.1186/s12934-026-02972-5","DOIUrl":"10.1186/s12934-026-02972-5","url":null,"abstract":"","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Scalable secretory production of influenza A (H1N1) hemagglutinin HA1 in Pichia pastoris through expression and process optimization.","authors":"Zeliang Guo, Wenting Ding, Chendi Yang, Xiaoying Zhi, Yu Zhang, Fengjia Xi, Rongzeng Liu","doi":"10.1186/s12934-026-02985-0","DOIUrl":"10.1186/s12934-026-02985-0","url":null,"abstract":"","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1186/s12934-026-02986-z
Maria Gorczyca, Abinaya M G Ponmalar, Julia Matz, Jean-Marc Nicaud, Ewelina Celińska
{"title":"Phenotyping transcription factors-related genotypes in Y. lipolytica across a range of industrially relevant process parameters and chemical stress conditions.","authors":"Maria Gorczyca, Abinaya M G Ponmalar, Julia Matz, Jean-Marc Nicaud, Ewelina Celińska","doi":"10.1186/s12934-026-02986-z","DOIUrl":"10.1186/s12934-026-02986-z","url":null,"abstract":"","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response mechanisms of xylitol-producing Saccharomyces cerevisiae strains to acetic acid and furfural and the role of SPI1, CTT1, and CLB1 in tolerance.","authors":"Yu-Ping Xia, Xin-Yu Wang, Bai-Xue Yang, Cai-Yun Xie, Yue-Qin Tang","doi":"10.1186/s12934-026-02987-y","DOIUrl":"10.1186/s12934-026-02987-y","url":null,"abstract":"","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-16DOI: 10.1186/s12934-026-02980-5
Gilberto Pérez-Morales, Enrique Merino, Miguel A Cevallos, Guillermo Gosset, Cuauhtémoc Licona-Cassani, Luis Caspeta, Alfredo Martinez
{"title":"Toward a systems metabolic engineering approach to improve thermotolerance of Escherichia coli.","authors":"Gilberto Pérez-Morales, Enrique Merino, Miguel A Cevallos, Guillermo Gosset, Cuauhtémoc Licona-Cassani, Luis Caspeta, Alfredo Martinez","doi":"10.1186/s12934-026-02980-5","DOIUrl":"10.1186/s12934-026-02980-5","url":null,"abstract":"","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-14DOI: 10.1186/s12934-026-02981-4
Reem M Farsi, Rasha A Metwally
{"title":"Marine Klebsiella sp. RR1-mediated AgNPs functionalized with matcha: synthesis, characterization, and evaluation of antibacterial, antioxidant, anti-inflammatory, and gene regulation of breast cancer potentials.","authors":"Reem M Farsi, Rasha A Metwally","doi":"10.1186/s12934-026-02981-4","DOIUrl":"10.1186/s12934-026-02981-4","url":null,"abstract":"","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12DOI: 10.1186/s12934-026-02952-9
Amira A El-Fallal, Mahmoud M Nour El-Dein, Shimaa R El-Esseily, Nancy M Mansour, Mohamed M El-Zahed
{"title":"Antimicrobial, antibiofilm, DNA binding, and antioxidant activities of green synthesized zinc oxide nanoparticles using the wild mushroom Lepista sordida (Schumach) singer EGDA2.","authors":"Amira A El-Fallal, Mahmoud M Nour El-Dein, Shimaa R El-Esseily, Nancy M Mansour, Mohamed M El-Zahed","doi":"10.1186/s12934-026-02952-9","DOIUrl":"10.1186/s12934-026-02952-9","url":null,"abstract":"","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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