Evidence map›Paper›PMID 41888881›Full record

ArticleMicrobial cell factories2026

Metabolic engineering of Streptomyces albulus for de novo serotonin production.

Yuan Zhang, Aoxiang Liu, Min Zhang, Jiabei Song, Qian Wang, Yongxuan Liu, Qingshou Yao, Linghui Kong, Xiuwen Wang, Jiayang Qin

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Article in Microbial cell factories, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Yuan Zhang *School of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Aoxiang Liu *School of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Min Zhang *School of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Jiabei SongSchool of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Qian WangSchool of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Yongxuan LiuSchool of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Qingshou YaoSchool of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Linghui KongSchool of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Xiuwen WangSchool of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Jiayang QinSchool of Pharmacy, Binzhou Medical University, Yantai, 264003, China. qinjy@bzmc.edu.cn.

Funding

National Natural Science Foundation of China 32370094
6 · The paper itself

Abstract

backgroundSerotonin (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.

resultsTo 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.

conclusionsThis 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.

Indexed as

Metabolic EngineeringSerotoninStreptomycesEscherichia coliFermentationTryptophanTryptophan HydroxylaseSerotoninTryptophanTryptophan HydroxylaseBiosynthesisFed-batchMetabolic engineeringMulti-enzyme cascadeSerotoninStreptomyces albulus

Identifiers

PMID41888881
PMCPMC13141384

What Socratic holds

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.