Tongqing Yang , Yixun Jiang , Tianyu Dong , Haoyu Liu , Ying Wang , Wenhai Xiao , Mingdong Yao
{"title":"Engineering the cytochrome P450 to enhance parthenolide production in Saccharomyces cerevisiae","authors":"Tongqing Yang , Yixun Jiang , Tianyu Dong , Haoyu Liu , Ying Wang , Wenhai Xiao , Mingdong Yao","doi":"10.1016/j.synbio.2025.04.006","DOIUrl":"10.1016/j.synbio.2025.04.006","url":null,"abstract":"<div><div>Parthenolide is confirmed to be an important component of the anticancer drug—ACT001. However, parthenolide biosynthesis in <em>Saccharomyces cerevisiae</em> (<em>S. cerevisiae</em>) was greatly hindered by the low conversion rate of its precursor, costunolide. In this study, the Position Specific Scoring Matrix (PSSM) was used to analyze the sequence evolutionary information of parthenolide synthase from <em>Tanacetum parthenium</em> (TpPTS), and a series of mutants were designed and validated. Notably, when the mutant of TpPTS—Y22G was introduced in <em>S. cerevisiae</em>, the parthenolide titer increased by 110 % compared to that of the TpPTS wild-type. Considering TpPTS as an endoplasmic reticulum-localized cytochrome P450 and the importance of heme supply, endoplasmic-associated molecular chaperone HRD1 (hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1) and heme biosynthesis gene HEM2 (aminolevulinate dehydratase) were overexpressed in <em>S. cerevisiae</em> to improve TpPTS expression and catalytic activity. As a result, a titer of 27.08 mg/L parthenolide was achieved in a shake flask, which was further increased by 209 %. Additionally, the conversion rate of costunolide to parthenolide increased from 20.4 % to 51.8 % compared to the initial strain yYTQ001. Eventually, a parthenolide titer of 99.71 mg/L was achieved in a 5-L bioreactor. Our research provides effective strategies and valuable references for engineering rate-limiting cytochrome P450 enzymes to improve sesquiterpenes production in <em>S. cerevisiae</em>.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 950-958"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934860","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}
Qi Xu, Ying Zhou, Qingjiang Sun, Xiangwei Zhao, Zuhong Lu, Kun Bi
{"title":"DNA-CTMF: Reconstruct high quality image from lossy DNA storage via Pixel-Base codebook and median filter","authors":"Qi Xu, Ying Zhou, Qingjiang Sun, Xiangwei Zhao, Zuhong Lu, Kun Bi","doi":"10.1016/j.synbio.2025.04.015","DOIUrl":"10.1016/j.synbio.2025.04.015","url":null,"abstract":"<div><div>Limited by uncertain base errors in DNA storage, additional correction measures may introduce redundancy or even expand errors, resulting in poor reconstructed image. DNA-CTMF is proposed to reconstruct high quality images at high errors and indels. Firstly, Pixel-Base codebook and chaotic system ensure DNA sequences meet biological constraints. Then, codebook adjusts offset base-groups affected by indels to their original position. Finally, median filter removes salt-and-pepper noise caused by base errors. Simulated experiments show reconstructed images by DNA-CTMF exhibit high quality with minimal variation at different error compositions. Even at 5 % error rate and indels accounting for 2/3, DNA-CTMF reconstruct high quality images with PSNR approximately 23 and MS-SSIM exceeding 0.9. Tests on 4000 images demonstrate DNA-CTMF's superiority on multiple images. Wet experiments proves that DNA-CTMF can reconstruct images close to original at low error rate, which is consistent with the results of simulated experiments. Different from researches which adopted error correction codes, DNA-CTMF addresses base errors by image processing technology, providing a new interdisciplinary solution and perspective for storing images into DNA.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 925-935"},"PeriodicalIF":4.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923627","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}
Shushu Chen , Mengyao Zhang , Xiaoyan Wu , Fan Bai , Linhui Gao , Yiwei Shen , Shaohua Dou , Peng Cai , Yongjin J. Zhou
{"title":"Promoter engineering for enhanced 3-hydroxypropionic acid production in Pichia pastoris","authors":"Shushu Chen , Mengyao Zhang , Xiaoyan Wu , Fan Bai , Linhui Gao , Yiwei Shen , Shaohua Dou , Peng Cai , Yongjin J. Zhou","doi":"10.1016/j.synbio.2025.04.013","DOIUrl":"10.1016/j.synbio.2025.04.013","url":null,"abstract":"<div><div>Enabling tools are essential for facilitating the methanol bioconversion in <em>Pichia pastoris</em>. However, there is still a relative lack of promoters that can stably express high levels without being affected by the carbon source, which hinders the construction and modification of cell factories containing long metabolic pathways. This study mapped a gene expression intensity library of central metabolic pathways in <em>P. pastoris</em> under methanol and glucose conditions. Through modification of the upstream sequences of promoters, an artificial promoter P<sub><em>S2</em></sub> was developed with a strong intensity up to 90 % of P<sub><em>GAP</em></sub>. By using this promoter, we successfully constructed a hybrid pathway that integrates the β-alanine and malonyl-CoA pathways for the production of 3-hydroxypropionic acid. Further combining rational metabolic engineering strategies, such as optimizing gene copy numbers and blocking byproduct synthesis pathways, the engineered strains CHP9 and CHP20 achieved 3-HP titers of 23 g/L and 22 g/L by using methanol as the sole carbon source. These results indicate that adaptive strength of promoters can facilitate efficient chemical biosynthesis in methanol bioconversion by mitigating glucose repression effects. This work preliminarily explored the expression patterns of genes in the central metabolic pathways of <em>P. pastoris</em>, identified and characterized the intensities of various endogenous promoters, and extended the enabling toolbox for <em>P. pastoris</em>. This result also lays a foundation for the construction of microbial cell factories and the industrial production of 3-HP via methanol bioconversion.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 916-924"},"PeriodicalIF":4.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899444","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}
Song Gao , Weizhu Zeng , Dong Li , Sha Xu , Jingwen Zhou
{"title":"Ty retrotransposon element based multiple integration toolkit for Saccharomyces cerevisiae","authors":"Song Gao , Weizhu Zeng , Dong Li , Sha Xu , Jingwen Zhou","doi":"10.1016/j.synbio.2025.04.011","DOIUrl":"10.1016/j.synbio.2025.04.011","url":null,"abstract":"<div><div>Extra-high-level overexpression of single or multiple specific proteins by integrating specific genes in the genome is vital to achieve the stable and efficient production of target proteins and metabolites in <em>S. cerevisiae</em>. Five families of Ty elements in the genome of <em>S. cerevisiae</em> CEN.PK2-1D, which could have dozens to hundreds of copies, have been employed to achieve massive gene expression. By engineering nine selective markers, six of them (<em>TRP1</em>, <em>LEU2</em>, <em>URA3</em>, <em>HIS5</em>, <em>natMX</em> and <em>hphMX</em>) achieve stably high copy integration (>15 copies) at Ty sites. Fluorescence proteins and taxifolin biosynthesis pathway genes were overexpressed to verify the toolkit. The titer of protein phiYFP in the multiple integration strain reached 1.6 g/L (268.1 mg/g DCW), and its fluorescence intensity was 3.3 times higher than that in the episomal overexpression strain. For taxifolin biosynthesis, 14 genes were integrated into three different Ty sites using three selective markers from the toolkit, resulting in 277.6 mg/L taxifolin accumulation from glucose.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 887-896"},"PeriodicalIF":4.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887471","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}
Tingting Li , Huina Dong , Jinlong Li , Huiying Wang , Chunxiang Pu , Siyu Chen , Zhiying Yang , Xinyi Ren , Xuan Liu , Zhaoxia Jin , Dawei Zhang
{"title":"Extending dynamic and operational range of the biosensor responding to l-carnitine by directed evolution","authors":"Tingting Li , Huina Dong , Jinlong Li , Huiying Wang , Chunxiang Pu , Siyu Chen , Zhiying Yang , Xinyi Ren , Xuan Liu , Zhaoxia Jin , Dawei Zhang","doi":"10.1016/j.synbio.2025.04.012","DOIUrl":"10.1016/j.synbio.2025.04.012","url":null,"abstract":"<div><div><span>l</span>-carnitine is a quaternary amine compound essential for eukaryotic metabolism. It is mainly involved in the oxidative decomposition of medium-and long-chain fatty acids and provides energy for the body. Therefore, it is widely used in health care and food additives. As a pivotal transcriptional activator of <span>l</span>-carnitine metabolism, CaiF is notably activated by crotonobetainyl-CoA, a key intermediate product in the carnitine metabolic pathway. Capitalizing on this mechanism, a sophisticated biosensor was ingeniously developed. Nevertheless, it is worth mentioning that the biosensor currently exhibits a relatively restricted detection range, which results in some specific limitations in practical application scenarios. In this paper, we constructed a biosensor based on CaiF and developed a strategy for modifying this biosensor. The structural configuration of CaiF was formulated by computer-aided design, and the DNA binding site was simulated, which was verified by alanine scanning. Functional Diversity-Oriented Volume-Conservative Substitution Strategy of the key sites of CaiF was conducted to extend the dynamic range of the biosensor. The biosensor based on CaiF<sup>Y47W/R89A</sup>, which exhibited a considerably expanded concentration response range, from 10<sup>−4</sup> mM–10 mM, was obtained. The response range was 1000-fold wider and the output signal intensity was 3.3-fold higher to that of the control biosensor. These variants may have great value in improving the <span>l</span>-carnitine production process.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 897-906"},"PeriodicalIF":4.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886845","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}
Yilei Han , Xuwei Ding , Junjian Tan , Yajuan Sun , Yunjiang Duan , Zheng Liu , Gaowei Zheng , Diannan Lu
{"title":"Sequence and taxonomic feature evaluation facilitated the discovery of alcohol oxidases","authors":"Yilei Han , Xuwei Ding , Junjian Tan , Yajuan Sun , Yunjiang Duan , Zheng Liu , Gaowei Zheng , Diannan Lu","doi":"10.1016/j.synbio.2025.04.014","DOIUrl":"10.1016/j.synbio.2025.04.014","url":null,"abstract":"<div><div>Recent advancements in data technology offer immense opportunities for the discovery and development of new enzymes for the green synthesis of chemicals. Current protein databases predominantly prioritize overall sequence matches. The multi-scale features underpinning catalytic mechanisms and processes, which are scattered across various data sources, have not been sufficiently integrated to be effectively utilized in enzyme mining. In this study, we developed a sequence- and taxonomic-feature evaluation driven workflow to discover enzymes that can be expressed in <em>E. coli</em> and catalyze chemical reactions <em>in vitro</em>, using alcohol oxidase (AOX) for demonstration, which catalyzes the conversion of methanol to formaldehyde. A dataset of 21 reported AOXs was used to construct sequence scoring rules based on features, including sequence length, structural motifs, catalytic-related residues, binding residues, and overall structure. These scoring rules were applied to filter the results from HMM-based searches, yielding 357 candidate sequences of eukaryotic origin, which were categorized into six classes at 85 % sequence similarity. Experimental validation was conducted in two rounds on 31 selected sequences representing all classes. Among these selected sequences, 19 were expressed as soluble proteins in <em>E. coli</em>, and 18 of these soluble proteins exhibited AOX activity, as predicted. Notably, the most active recombinant AOX exhibited an activity of 8.65 ± 0.29 U/mg, approaching the highest activity of native eukaryotic enzymes. Compared to the established UniProt-annotation-based workflow, this feature-evaluation-based approach yielded a higher probability of highly active recombinant AOX (from 8.3 % to 19.4 %), demonstrating the efficiency and potential of this multi-dimensional feature evaluation method in accelerating the discovery of active enzymes.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 907-915"},"PeriodicalIF":4.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886847","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}
Bin Wang , Yaokang Wu , Xueqin Lv , Long Liu , Jianghua Li , Guocheng Du , Jian Chen , Yanfeng Liu
{"title":"T7 RNA polymerase-guided base editor for accelerated continuous evolution in Bacillus subtilis","authors":"Bin Wang , Yaokang Wu , Xueqin Lv , Long Liu , Jianghua Li , Guocheng Du , Jian Chen , Yanfeng Liu","doi":"10.1016/j.synbio.2025.04.010","DOIUrl":"10.1016/j.synbio.2025.04.010","url":null,"abstract":"<div><div>Targeted <em>in vivo</em> hypermutation mediated by base deaminase-T7 RNA polymerase (T7 RNAP) fusions promotes genetic diversification and accelerates continuous directed evolution. Due to the lack of a T7RNAP expression regulation system and functionally compatible linker for fusion protein expression, T7RNAP-guided continuous evolution has not been established in <em>Bacillus subtilis</em>, which limited long gene fragment continuous evolution targeted on genome. Here, we developed BS-MutaT7 system, which introduced mutations into specific genomic regions by leveraging chimeric fusions of base deaminases with T7RNAP in <em>B. subtilis.</em> We selected seven different sources of adenosine and cytosine deaminases, 14 fusion protein linkers to be fused with T7RNAP, constructing four libraries with the size of 5000, where deaminases were fused at either the N- or C-terminus of T7RNAP. Based on the efficiency of binding to T7 promoter and high mutagenesis activity, two optimal chimeric mutators, BS-MutaT7<sup>A</sup> (TadA8e-Linker0-T7RNAP) and BS-MutaT7<sup>C</sup> (PmCDA1-(GGGGS)<sub>3</sub>-T7RNAP co-expressed with UGI) were identified. The target mutation rates reached 1.2 × 10<sup>−5</sup> per base per generation (s.p.b.) and 5.8 × 10<sup>−5</sup> s.p.b., representing 7000-fold and 37,000-fold increases over the genomic mutation rate, respectively. Both exhibited high processivity, maintaining mutation rates of 5.8 × 10<sup>−6</sup> s.p.b. and 2.9 × 10<sup>−5</sup> s.p.b. within a 5 kb DNA region. Notably, BS-MutaT7<sup>C</sup> exhibited superior mutagenic activity, making it well-suited for applications requiring intensive and sustained genomic diversification. Application of BS-MutaT7 enabled a 16-fold increase in tigecycline resistance and enhanced β-lactoglobulin (β-Lg) expression by evolving the global transcriptional regulator <em>codY</em>, achieving a β-Lg titer of 3.92 g/L. These results highlight BS-MutaT7 as a powerful and versatile tool for genome-scale continuous evolution in <em>B. subtilis</em>.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 876-886"},"PeriodicalIF":4.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887470","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}
Jiyun Lou , Xia Wang , Runxia Li , Jun Yao , Junpeng Hu , Xianwu Qin , Mingjie Jin , Shihui Yang
{"title":"Integration of metabolic and evolutionary processes to construct efficient xylose-utilizing strain of Zymomonas mobilis for lignocellulosic ethanol production","authors":"Jiyun Lou , Xia Wang , Runxia Li , Jun Yao , Junpeng Hu , Xianwu Qin , Mingjie Jin , Shihui Yang","doi":"10.1016/j.synbio.2025.04.009","DOIUrl":"10.1016/j.synbio.2025.04.009","url":null,"abstract":"<div><div>Xylose is a major component of lignocellulose, and it is crucial to enable microorganisms the capability of efficient xylose utilization for economical lignocellulosic biochemical production. <em>Zymomonas mobilis</em> is a natural ethanologenic bacterium with xylose-utilizing recombinant strains engineered for commercial lignocellulosic ethanol production. However, low efficiency of xylose utilization is still the major hurdle for lignocellulosic biochemical production, especially in the lignocellulosic hydrolysate containing inhibitory compounds and mixed sugars of glucose and xylose. In this study, xylose-utilization capability of a xylose-utilizing recombinant strain 8b-S38 of <em>Z. mobilis</em> was further improved by evaluating the effects of different xylose metabolic pathways, xylose isomerases, and xylose transporters. The results demonstrated that xylose isomerase pathway is still the most efficient one in <em>Z. mobilis</em> among the xylose metabolic pathways examined, and the introduction of xylose isomerase (XI) such as StrXI and PanXI to increase its copy numbers can improve xylose utilization. In addition, the introduction of effective xylose transporter such as high-affinity xylose transporter XylFGH and the glucose facilitator mutant Glf<sup>A165M−K458I</sup> promoted xylose transportation and subsequent utilization. A recombinant strain S67SPGlf<sup>m</sup> was constructed combining rational engineering of xylose isomerases and transporters and semi-rational adaptation, which exhibited enhanced xylose utilization capability in lignocellulosic hydrolysate. This study illustrated that the construction of robust and efficient industrial strains with complex phenotypes requires a combination of different strategies such as metabolic engineering and adaptive laboratory evolution, which also provided biological parts such as xylose isomerases and xylose transporters to help design and construct microbial cell factories for efficient xylose utilization in the future.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 858-867"},"PeriodicalIF":4.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869540","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}
Ziyue Guo , Xin Zhang , Lin Zhou , Qungang Huang , Qianjin Kang , Linquan Bai
{"title":"Nonglycosidic C–O bond formation catalyzed by a bifunctional pseudoglycosyltransferase ValL","authors":"Ziyue Guo , Xin Zhang , Lin Zhou , Qungang Huang , Qianjin Kang , Linquan Bai","doi":"10.1016/j.synbio.2025.04.007","DOIUrl":"10.1016/j.synbio.2025.04.007","url":null,"abstract":"<div><div>The C<sub>7</sub>N antibiotic validamycin A is an antifungal agent widely used as a crop protectant. It comprises a validoxylamine A unit linked to a glucose moiety, which is formed through a nonglycosidic <em>C</em><em>–</em><em>N</em> bond connecting a valienol moiety and a validamine moiety, a reaction catalyzed by the pseudoglycosyltransferase ValL. In this study, we analyzed the chemical composition of validamycins in <em>Streptomyces hygroscopicus</em> var. <em>jinggangensis</em> TL01. A series of novel oxygen-bridged analogues, namely, validenomycin, validomycin, and 1,1′-bis-valienol, were identified in the culture supernatants, and their chemical structures were elucidated using a combination of one- and two-dimensional nuclear magnetic resonance and mass spectrometry. Gene disruption and complementation experiments revealed that <em>valL</em> is essential for the biosynthesis of these new oxygen-bridged analogues of validamycins. Biochemical assays further demonstrated that ValL catalyzed the <em>C–O</em> bond formation between GDP-valienol and valienol-7-phosphate, producing 1,1′-bis-valienol-7-phosphate, which was subsequently dephosphorylated by ValO and glycosylated by ValG to yield validenomycin. Collectively, our findings revealed the unique ability of ValL to catalyze nonglycosidic <em>C–O</em> coupling, potentially enabling the generation of various chemical scaffolds for C<sub>7</sub>N family antibiotics.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 846-857"},"PeriodicalIF":4.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864111","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}
Ying Wang , Ruosi Zhang , Mingdong Yao , Wenhai Xiao , Ying Wang , Ying-Jin Yuan
{"title":"Transcriptomic studies on the product stress response revealed that YCF1 is a beneficial factor for progesterone production in Yarrowia lipolytica","authors":"Ying Wang , Ruosi Zhang , Mingdong Yao , Wenhai Xiao , Ying Wang , Ying-Jin Yuan","doi":"10.1016/j.synbio.2025.04.008","DOIUrl":"10.1016/j.synbio.2025.04.008","url":null,"abstract":"<div><div>Progesterone is a widely used therapeutic hormone and a common precursor for the synthesis of pharmaceutical steroids in both mammals and plants. It has been successfully produced in heterologous microorganisms, but the market demand has not been met. The low progesterone yield, possibly due to product stress, may put pressure on the growth of strains and limit product synthesis efficiency. In this study, key pathways and genes that cause changes in amino acid and lipid metabolism and protein transport were identified through omics analysis. The expression of transporters leads to increased progesterone production and alleviated growth inhibition. Two related genes (gene IDs: 2912325 and 2908366) encoding the transporters glpF and SNQ2 improved production by 29.2 % and 51.7 %, respectively. Isoenzymes of native and exogenous transporters were screened and overexpressed. YCF1 from <em>Saccharomyces cerevisiae</em> exhibited the greatest benefit, increasing progesterone synthesis by 69.6 %. Our findings help reveal the impact of product stress on cellular metabolism and processes, providing research directions and literature support for the synthesis of other products.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1087-1097"},"PeriodicalIF":4.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271522","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}