Synthetic and Systems Biotechnology最新文献

{"title":"Engineering an ATP-saving mevalonate pathway for high-efficiency S-(+)-linalool production in Serratia marcescens","authors":"Yue Chen ,&nbsp;Linbo Gou ,&nbsp;Di Liu ,&nbsp;Shengfang Wu ,&nbsp;Xiuwen Zhou ,&nbsp;Tai-Ping Fan ,&nbsp;Long Wang ,&nbsp;Yujie Cai","doi":"10.1016/j.synbio.2025.11.010","DOIUrl":"10.1016/j.synbio.2025.11.010","url":null,"abstract":"<div><div>(S)-(+)-linalool, a valuable acyclic monoterpenol secondary metabolite of plants, finds extensive applications in the food, flavor and fragrance, pharmaceutical, and daily chemical industries. Microbial synthesis offers two pathways for its production, among which the mevalonate (MVA) pathway derived from halophilic archaea is more widely employed. However, the traditional Haloarchaea-type MVA pathway relies on bifunctional enzyme catalysis, consuming 3 molecules of ATP. Moreover, the catalytic activity of natural linalool synthase (LIS) is generally low, failing to meet industrial requirements. Additionally, linalool exhibits significant toxicity to microbial hosts, thereby limiting the production capacity of conventional chassis microorganisms. To address these bottlenecks, this study implemented systematic optimizations: Firstly, the Archaeal mevalonate pathway was reconstructed by replacing the original bifunctional enzyme with two monofunctional enzymes, successfully reducing ATP consumption to 2 molecules. Secondly, through directed screening and rational design, a high-activity linalool synthase mutant, CsMLIS^I331V/I444L, derived from <em>Coriandrum sativum</em>, was obtained. Furthermore, an enzyme fusion strategy was adopted, involving the introduction of a long flexible linker between key genes, which significantly enhanced catalytic efficiency. Finally, <em>S</em>. <em>marcescens</em> HBQA7Δ<em>sIaAB-pyc</em>, a strain previously screened in our laboratory with broad-spectrum tolerance to terpenoids, was selected as the novel chassis cell. Collectively, these efforts resulted in the construction of a microbial cell factory for the efficient synthesis of (S)-(+)-linalool, laying a solid foundation for industrial-scale production.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 124-133"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programmable large-cargo integration: Overcoming size constraints for next-generation gene therapy","authors":"Lifang Yu ,&nbsp;Mario Andrea Marchisio","doi":"10.1016/j.synbio.2025.11.008","DOIUrl":"10.1016/j.synbio.2025.11.008","url":null,"abstract":"<div><div>The emergence of base and prime editors—genome editing tools that avoid double-strand breaks (DSBs)—has enabled precise point mutations, insertions, inversions, deletions, and substitutions, which accelerates the development of single-intervention therapies and advances individualized genomic medicine. However, their limited efficiency in inserting large DNA fragments has restricted applications for correcting diverse pathogenic mutations within a single gene. In this review, we explore three recently developed strategies for efficient large DNA cargo insertion (&gt;1 kb): CRISPR-associated Tn7-like transposases (CASTs), PE-integrase systems, and R2 retrotransposon fusions (nCas9-R2). We examine the applications of these systems in both bacterial and mammalian contexts and discuss their respective advantages and current limitations. Finally, we address persistent challenges and propose potential directions to guide future research.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 101-114"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics elucidation of resource allocation for enhanced ethanol production via precise glucose control in anaerobic Saccharomyces cerevisiae fermentation","authors":"Zhihao Liu ,&nbsp;Linghong Zheng ,&nbsp;Xiaofei Yu ,&nbsp;Yingping Zhuang ,&nbsp;Guan Wang","doi":"10.1016/j.synbio.2025.10.015","DOIUrl":"10.1016/j.synbio.2025.10.015","url":null,"abstract":"<div><div>Ethanol, a high-demand clean energy source, is primarily produced via fed-batch fermentation in industrial settings. Although our previous study identified an optimal glucose concentration of 30 g/L for maximal ethanol yield, the mechanisms underlying glucose-dependent cellular adaptation remain unclear. Here, we performed an integrated multi-omics analysis, including transcriptomics, proteomics, metabolomics, and fluxomics, to compare yeast cells under glucose-controlled and uncontrolled conditions. Our results indicate that high glucose stress triggers the regulation of transporters with different affinities and the upregulation of heat shock proteins (HSPs), trehalose, and amino acids. In contrast, protein turnover was reduced under glucose-controlled conditions, suggesting more efficient resource allocation. This metabolic reallocation enhances carbon flux through glycolysis, potentially providing additional energy and NADH to support biomass growth and ethanol production. These findings advance our understanding of yeast regulatory mechanisms under glucose stress and provide insights for metabolic engineering and process optimization.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 20-31"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing delta-tocotrienol production in Saccharomyces cerevisiae via metabolic engineering strategies in conjunction with the mutagenesis of tocopherol cyclase","authors":"Ziming Liu ,&nbsp;Min Tang ,&nbsp;Wanze Zhang ,&nbsp;Yanjie Tian ,&nbsp;Jianjun Qiao ,&nbsp;Mingzhang Wen ,&nbsp;Weiguo Li ,&nbsp;Qinggele Caiyin","doi":"10.1016/j.synbio.2025.11.013","DOIUrl":"10.1016/j.synbio.2025.11.013","url":null,"abstract":"<div><div>Delta (δ)-tocotrienol is a member of the vitamin E family and exhibits bioactivities such as antioxidant, anti-inflammatory, and neuroprotective activities. As a nutrient with protective effects on human health, δ-tocotrienol has broad application prospects in food, cosmetic, and pharmaceutical industries. The construction of efficient microbial cell factories capable of δ-tocotrienol production using synthetic biology approaches is an effective strategy for supplementing or even replacing the vitamin E supply chain in the future. The current study successfully enhanced the biosynthesis of δ-tocotrienol in <em>Saccharomyces cerevisiae</em> by combining metabolic engineering and enzyme engineering strategies. Specifically, the substrate channel constructed by the sequential fusion of the enzymes PaCrtE and SyHPT successfully increased the supply of the key precursor MGGBQ, resulting in a significant increase in the production of δ-tocotrienol. <em>In situ</em> extraction and optimization of the expression of transporter protein PDR1 increased the efflux of δ-tocotrienol, directing the metabolic flux toward the product δ-tocotrienol. To enhance the catalytic activity of the key rate-limiting enzyme tocopherol cyclase from <em>Arabidopsis thaliana</em> (AtTC), semirational protein design was conducted herein. The mutant AtTC^T87S was found to increase the production of δ-tocotrienol by 2.3 times compared to that obtained with the wild-type enzyme. AtTC^T87S can thus be universally used for synthetic biology strategies in future studies to enhance the microbial heterologous production of δ-tocotrienol. The strain T08 was finally obtained herein; the numerous metabolic engineering strategies discussed in this study were integrated into this strain, allowing the production of 4337.3 μg/L of δ-tocotrienol in a shake-flask fermentation, which is 8.9 times that of the yield obtained with the initial strain T03. Scaling up to a 5-L fermentation tank resulted in a δ-tocotrienol yield of 16.9 mg/L.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 172-182"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145747943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formatotrophic Komagataella phaffii expressing recombinant xylanase via metabolic engineering","authors":"Ziwei Zhou ,&nbsp;Bing Liu ,&nbsp;Wenjie Cong ,&nbsp;Hualan Zhou ,&nbsp;Yu Zheng ,&nbsp;Jianguo Zhang","doi":"10.1016/j.synbio.2025.11.015","DOIUrl":"10.1016/j.synbio.2025.11.015","url":null,"abstract":"<div><div>Formate utilization as a sustainable carbon source for microbial production of high-value chemicals and heterologous proteins presents considerable safety and environmental benefits over conventional feedstocks. As a low-cost, CO₂-derived compound, formate serves as a non-flammable and non-toxic alternative to methanol for induction of recombinant expression in <em>Komagataella phaffii</em>. However, since native <em>K. phaffii</em> only utilizes formate as an energy source rather than a carbon substrate for biomass synthesis, we engineered a synthetic peroxisomal formate assimilation pathway by introducing heterologous acetyl-CoA synthetase (ACS) and acetaldehyde dehydrogenase (ACDH), thereby enabling formatotrophic growth with formate as the sole carbon source. This chassis was further optimized through (i) co-expression of the transcriptional activator Mit1 to enhance the coupling efficiency of the ACS-ACDH module, and (ii) reinforcement of the Xu5P pathway by overexpressing dihydroxyacetone synthase (DAS1) and ribulose-5-phosphate-3-epimerase (RPE) to redirect metabolic flux. The resulting formatotrophic <em>K. phaffi</em> strain achieved a specific growth rate of 0.012 h⁻¹ in basal salt medium with formate as the sole carbon source, and produced 30.9 U/(mL·OD₆₀₀) of xylanase from <em>Aspergillus niger</em> ATCC 1015 as a model heterologous protein. Furthermore, ¹³C isotopic tracing confirmed the incorporation of formate-derived carbon into central metabolism for the biosynthesis of amino acids, nucleotides, and structural carbohydrates, validating active formate assimilation. This study establishes a microbial platform for formate-based production of heterologous proteins and underscores the potential of metabolic engineering to advance sustainable biomanufacturing from one-carbon feedstocks.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 185-196"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic-free high-yield (-)-α-bisabolol production in Serratia marcescens via metabolic engineering and genomic integration of mevalonate pathway genes","authors":"Wei Li ,&nbsp;Di Liu ,&nbsp;Linbo Gou ,&nbsp;Shengfang Wu ,&nbsp;Xiuwen Zhou ,&nbsp;Tai-Ping Fan ,&nbsp;Long Wang ,&nbsp;Yujie Cai","doi":"10.1016/j.synbio.2025.12.011","DOIUrl":"10.1016/j.synbio.2025.12.011","url":null,"abstract":"<div><div>(-)-α-Bisabolol, a valuable monocyclic sesquiterpene alcohol, has garnered significant attention in the pharmaceutical and cosmetic industries due to its remarkable anti-inflammatory, antibacterial, and skin-care properties. In this study, <em>Serratia marcescens</em> HBQA7 (<em>S. marcescens</em> HBQA7), a non-model strain resistant to terpenoid toxicity, was used as the production host, and the expression intensities of different integration sites were screened. The complete (-)-α-bisabolol synthesis pathway was integrated into these sites, achieving a production titer of 3.5 g L⁻¹. On this basis, by knocking out competitive pathway genes (such as <em>slaB</em> and <em>adhE</em>) and global regulatory factors (<em>arcA</em> and <em>iclR</em>), and introducing efficient glucose transport and activation (<em>glf</em> and <em>glk</em>), the shake flask fermentation titer was increased to 7.21 g L⁻¹. Through optimization of fermentation culture by orthogonal experiments and others, the titer was further increased to 9.90 g L⁻¹. Finally, through the fed-batch fermentation process conducted in a 50 L bioreactor, a titer of 102.3 g L⁻¹ was achieved after 110 h of cultivation. The productivity reached 0.93 g L⁻¹ h⁻¹. This study not only establishes the most efficient microbial production system for (-)-α-bisabolol reported to date, but also demonstrates the outstanding potential of <em>S. marcescens</em> as a chassis for terpenoid biosynthesis. It provides a novel strategy for the industrial production of high-value terpenoids.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 274-283"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming of abscisic acid-producing strain Botrytis cinerea TB-31 toward terpenoid biosynthesis using a CRISPR/Cas9 ribonucleoprotein system","authors":"Xiao-Nan Hou ,&nbsp;Dan Shu ,&nbsp;Tian-Fu Li ,&nbsp;Qi Yang ,&nbsp;Zhe-Min Li ,&nbsp;Di Luo ,&nbsp;Jie Yang ,&nbsp;Zhi-Ying Yan ,&nbsp;Hong Tan","doi":"10.1016/j.synbio.2025.12.002","DOIUrl":"10.1016/j.synbio.2025.12.002","url":null,"abstract":"<div><div>Compared with conventional microbial hosts, filamentous fungi have distinct advantages for the industrial-scale biosynthesis of high-value chemical compounds. However, current research on strain engineering and fermentation optimization strategies for synthetic biology applications is limited in filamentous fungi, especially in industrial production strains. In this study, we established a CRISPR/Cas9-based gene editing system in <em>Botrytis cinerea</em> strain TB-31, an important filamentous fungal platform for the study of the biosynthesis and regulation of the sesquiterpenoid abscisic acid (ABA). This system enables efficient single- and multigene knockout, large-fragment deletion, and heterologous protein expression. Among the engineered mutant strains, the △<em>bcaba1234</em> strain with complete ablation of the ABA biosynthetic gene cluster (BGC) demonstrated significant metabolic flux rewiring, redirecting cellular resources toward terpenoid precursor biosynthesis; this metabolic reprogramming proves pivotal for high-value terpenoid biosynthesis. This study not only establishes an efficient genome editing tool for the ABA-producing strain <em>B. cinerea</em> TB-31 but also provides a foundation for its development as a new potential terpenoid-producing chassis strain.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 238-254"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfer learning with pre-trained language models for protein expression level prediction in Escherichia coli","authors":"Chunhe Yang ,&nbsp;YuLing Zhao ,&nbsp;Ruoyu Wang ,&nbsp;Haoran Li ,&nbsp;Xiaoping Liao ,&nbsp;Hongwu Ma","doi":"10.1016/j.synbio.2025.11.012","DOIUrl":"10.1016/j.synbio.2025.11.012","url":null,"abstract":"<div><div>Accurately predicting recombinant protein expression in <em>Escherichia coli</em> remains a long-standing challenge due to the multifactorial nature of gene regulation and translation. Existing computational approaches typically emphasize either codon usage or protein sequence features, limiting predictive accuracy and generalizability. Here we present TLCP-EPE, a transfer learning framework that, for the first time, fuses codon- and protein-level pre-trained language models to jointly capture determinants of expression. By fine-tuning CaLM and ProtT5 with low-rank adaptation (LoRA) and integrating their embeddings through a BiGRU-MLP predictor, TLCP-EPE learns expression-aware representations that outperform state-of-the-art methods. Across two independent test datasets, TLCP-EPE achieved robust performance (AUC 0.835 on codon data; AUC 0.713 on protein data), consistently surpassing conventional codon-based metrics and deep learning baselines. Our results demonstrate that dual-modal modeling of codon and protein sequences enables more accurate and generalizable prediction of expression levels, providing a powerful foundation for rational protein design and biomanufacturing applications.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 115-123"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modifying the upstream open reading frames of cellulase gene enhances cellulase production in Penicillium oxalicum","authors":"Shuai Zhao ,&nbsp;Xin Shen ,&nbsp;Ting-Yu Zhou ,&nbsp;Yan-Hao Zhao ,&nbsp;Di Tian ,&nbsp;Xue-Mei Luo ,&nbsp;Zhi-Peng Zhou ,&nbsp;Xin-Qing Zhao ,&nbsp;Jia-Xun Feng","doi":"10.1016/j.synbio.2025.12.016","DOIUrl":"10.1016/j.synbio.2025.12.016","url":null,"abstract":"<div><div>Cellulase plays an irreplaceable role in biomanufacturing using plant biomass as feedstock. However, improving cellulase production by fungi through manipulation of upstream open reading frames (uORFs) in the 5′-untranslated regions (5′-UTR) of cellulase genes has been less frequently explored. This study aimed to screen uORFs in the 5′-UTR of cellulase genes in <em>Penicillium oxalicum</em>, identify functional uORFs in the 5′-UTR of the <em>eg1</em> gene which encodes a key endo-β-1,4-glucanase (EG) in <em>P</em>. <em>oxalicum</em>, and enhance fungal cellulase production through uORF modifications. Among the 25 cellulase genes examined in <em>P</em>. <em>oxalicum</em> strain HP7-1, 23 contained uORFs in their 5′-UTR. Seven uORFs were annotated in the 5′-UTR of the <em>eg1</em> gene. A uORF-green fluorescent protein (GFP) reporter system demonstrated that uORF1 and uORF3 inhibited, while uORF7 enhances, GFP abundance. Overexpression of <em>eg1</em> containing uORF1 or uORF3 variants where the start codon of the uORF was mutated to AAG in <em>P</em>. <em>oxalicum</em> led to a significant 91.7 % and 62.1 % average increase in carboxymethyl cellulase production after 4 days of induction compared to the start strain Δ<em>PoxKu70</em>. Real-time quantitative reverse transcription-polymerase chain reaction, mRNA stability determination, and <em>in vitro</em> translation experiments collectively revealed that these three uORFs influence the mRNA stability of the downstream mORF, but not translation efficiency. These findings highlight the critical role of uORFs in regulating gene expression during fungal enzyme biosynthesis and offer a valuable alternative strategy for improving enzyme production.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 383-392"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic engineering enables Escherichia coli to grow on 1,3-propanediol","authors":"Nga Yu Poon ,&nbsp;Anthony J. Sinskey ,&nbsp;Kang Zhou","doi":"10.1016/j.synbio.2025.11.009","DOIUrl":"10.1016/j.synbio.2025.11.009","url":null,"abstract":"<div><div>1,3-propanediol (1,3-PDO) is used to synthesize plastics used in many consumer products. As the demand and production of such plastics increase, a technology will be needed to utilize 1,3-PDO released from the plastics after their disposal. In our previous study, we developed the strain (<strong>BA07Δ</strong>) that could use malonate semialdehyde (MSA, an important intermediate in the 1,3-PDO assimilation pathway) as the major carbon source. Here, we present construction of <strong>PA16</strong>, a strain which could grow to an OD₆₀₀ of 7 by consuming 6.5 g/L of 1,3-PDO within 72 h in M9-based medium supplemented with 1 g/L of complete supplement mixture (CSM). This was achieved by adaptive laboratory evolution (ALE) after extending the pathway in <strong>BA07Δ</strong> through the introduction of a 1,3-propanediol dehydrogenase from <em>Klebsiella pneumoniae</em> (KpDhaT), an aldehyde dehydrogenase from <em>E. coli</em> (EcPuuC) and a 3-hydroxypropionate dehydrogenase from <em>Halomonas bluephagenesis</em> (HbDddA). Comparing the transcriptome of <strong>PA16</strong> and its ancestor in the ALE (<strong>PA1</strong>) revealed the upregulation of two genes, threonine dehydrogenase (EcTdh) and 2-amino-3-ketobutyrate CoA ligase (EcKbl) responsible for threonine degradation. The overexpression of these genes in <strong>PA1</strong> resulted in a 5-fold increase in the 72-h cell density. This finding helped simplify the growth medium of <strong>PA16</strong>: the supplement mixture containing more than 10 amino acids/nucleobases was reduced to just having 0.1 g/L threonine. <strong>PA16</strong>'s OD₆₀₀ reached 3 when it grew in a defined medium containing 10 g/L 1,3-PDO and 0.1 g/L threonine as carbon sources. <em>E. coli</em> <strong>PA16</strong> should be a useful strain to the subsequent research on upcycling 1,3-PDO derived from plastic wastes.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 209-217"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}