Synthetic and Systems Biotechnology最新文献

{"title":"Biodegradation of combined pollutants of polyethylene terephthalate and phthalate esters by esterase-integrated Pseudomonas sp. JY-Q with surface-co-displayed PETase and MHETase","authors":"Haixia Wang,&nbsp;Jiahong Zhu,&nbsp;Meng Sun,&nbsp;Mengjie Gu,&nbsp;Xiya Xie,&nbsp;Tongtong Ying,&nbsp;Zeling Zhang,&nbsp;Weihong Zhong","doi":"10.1016/j.synbio.2024.08.001","DOIUrl":"10.1016/j.synbio.2024.08.001","url":null,"abstract":"<div><p>The waste pollution problem caused by polyethylene terephthalate (PET) plastics poses a huge threat to the environment and human health. As plasticizers, Phthalate esters (PAEs) are widely used in PET production and become combined pollutants with PET. Synthetic biology make it possible to construct engineered cells for microbial degradation of combined pollutants of PET and PAEs. PET hydroxylase (PETase) and monohydroxyethyl terephthalate hydroxylase (MHETase) isolated from <em>Ideonella sakaiensis</em> 201-F6 exhibit the capability to depolymerize PET. However, PET cannot enter cells, thus enzymatic degradation or cell surface displaying technology of PET hydrolase are the potential strategies. In this study, <em>Pseudomonas</em> sp. JY-Q was selected as a chassis strain, which exhibits robust stress tolerance. First, a truncated endogenous outer membrane protein cOmpA and its variant Signal (OprF)-cOmpA were selected as anchor motifs for exogenous protein to display on the cell surface. These anchor motifs were fused at the N-terminal of PET hydrolase and MHETase and transformed into <em>Pseudomonas</em> sp. JY-Q, the mutant strains successfully display the enzymes on cell surface, after verification by green fluorescent protein labeling and indirect immunofluorescence assay. The resultant strains also showed the catalytic activity of co-displaying PETase and MHETase for PET biodegradation. Then, the cell surface displaying PET degradation module was introduced to a JY-Q strain which genome was integrated with PAEs degrading enzymes and exhibited PAEs degradation ability. The resultant strain JY-Q-R1-R4-SFM-TPH have the ability of degradation PET and PAEs simultaneously. This study provided a promising strain resource for PET and PAEs pollution control.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 10-22"},"PeriodicalIF":4.4,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001054/pdfft?md5=1fdbf56b537e316202eda55af8357037&pid=1-s2.0-S2405805X24001054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963055","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":"Advances in the biosynthesis of tetraacetyl phytosphingosine, a key substrate of ceramides","authors":"Xin Zhang,&nbsp;Xiaochen Zhang,&nbsp;Lu Lin,&nbsp;Kaifeng Wang,&nbsp;Xiao-Jun Ji","doi":"10.1016/j.synbio.2024.07.005","DOIUrl":"10.1016/j.synbio.2024.07.005","url":null,"abstract":"<div><p>Ceramides, formed by the dehydration of long-chain fatty acids with phytosphingosine and its derivatives, are widely used in skincare, cosmetics, and pharmaceuticals. Due to the exceedingly low concentration of phytosphingosine in plant seeds, relying on the extraction method is highly challenging. Currently, the primary method for obtaining phytosphingosine is the deacetylation of tetraacetyl phytosphingosine (TAPS) derived from fermentation. <em>Wickerhamomyces ciferrii</em>, an unconventional yeast from the pods of <em>Dipteryx odorata</em>, is the only known microorganism capable of naturally secreting TAPS, which is of great industrial value. In recent years, research and applications focused on modifying <em>W. ciferrii</em> for TAPS overproduction have increased rapidly. This review first describes the discovery history, applications, microbial synthesis pathway of TAPS. Research progress in using haploid breeding, mutagenesis breeding, and metabolic engineering to improve TAPS production is then summarized. In addition, the future prospects of TAPS production using the <em>W. ciferrii</em> platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future researches are also emphasized.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 1-9"},"PeriodicalIF":4.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001030/pdfft?md5=4338020a04a9a2996fa35bac1c6c2c94&pid=1-s2.0-S2405805X24001030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962571","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":"Auxotrophy-based curation improves the consensus genome-scale metabolic model of yeast","authors":"Siyu Han ,&nbsp;Ke Wu ,&nbsp;Yonghong Wang ,&nbsp;Feiran Li ,&nbsp;Yu Chen","doi":"10.1016/j.synbio.2024.07.006","DOIUrl":"10.1016/j.synbio.2024.07.006","url":null,"abstract":"<div><p><em>Saccharomyces cerevisiae</em>, a widely utilized model organism, has seen continuous updates to its genome-scale metabolic model (GEM) to enhance the prediction performance for metabolic engineering and systems biology. This study presents an auxotrophy-based curation of the yeast GEM, enabling facile upgrades to yeast GEMs in future endeavors. We illustrated that the curation bolstered the predictive capability of the yeast GEM particularly in predicting auxotrophs without compromising accuracy in other simulations, and thus could be an effective manner for GEM refinement. Last, we leveraged the curated yeast GEM to systematically predict auxotrophs, thereby furnishing a valuable reference for the design of nutrient-dependent cell factories and synthetic yeast consortia.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 861-870"},"PeriodicalIF":4.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001042/pdfft?md5=e5f5c9703c432bcf1368afc6ab2ddb45&pid=1-s2.0-S2405805X24001042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952424","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":"Integrating chemistry knowledge in large language models via prompt engineering","authors":"Hongxuan Liu ,&nbsp;Haoyu Yin ,&nbsp;Zhiyao Luo ,&nbsp;Xiaonan Wang","doi":"10.1016/j.synbio.2024.07.004","DOIUrl":"10.1016/j.synbio.2024.07.004","url":null,"abstract":"<div><p>This paper presents a study on the integration of domain-specific knowledge in prompt engineering to enhance the performance of large language models (LLMs) in scientific domains. The proposed domain-knowledge embedded prompt engineering method outperforms traditional prompt engineering strategies on various metrics, including capability, accuracy, F1 score, and hallucination drop. The effectiveness of the method is demonstrated through case studies on complex materials including the MacMillan catalyst, paclitaxel, and lithium cobalt oxide. The results suggest that domain-knowledge prompts can guide LLMs to generate more accurate and relevant responses, highlighting the potential of LLMs as powerful tools for scientific discovery and innovation when equipped with domain-specific prompts. The study also discusses limitations and future directions for domain-specific prompt engineering development.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 23-38"},"PeriodicalIF":4.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001029/pdfft?md5=dd4b0bce2ec7b1ef7c85fdaea00ca13c&pid=1-s2.0-S2405805X24001029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963054","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":"Liposome-based RNAi delivery in honeybee for inhibiting parasite Nosema ceranae","authors":"Yue Qi ,&nbsp;Chen Wang ,&nbsp;Haoyu Lang ,&nbsp;Yueyi Wang ,&nbsp;Xiaofei Wang ,&nbsp;Hao Zheng ,&nbsp;Yuan Lu","doi":"10.1016/j.synbio.2024.07.003","DOIUrl":"10.1016/j.synbio.2024.07.003","url":null,"abstract":"<div><p><em>Nosema ceranae</em>, a parasite that parasitizes and reproduces in the gut of honeybees, has become a serious threat to the global apiculture industry. RNA interference (RNAi) technology can be used to inhibit <em>N. ceranae</em> growth by targeting silencing the thioredoxin reductase (TrxR) in <em>N. ceranae</em>. However, suitable carriers are one of the reasons limiting the application of RNAi due to the easy degradation of dsRNA in honeybees. As a vesicle composed of a lipid bilayer, liposomes are a good carrier for nucleic acid delivery, but studies in honeybees are lacking. In this study, liposomes were used for double-stranded RNA (dsRNA) dsTrxR delivery triggering RNAi to inhibit the <em>N. ceranae</em> growth in honeybees. Compared to naked dsTrxR, liposome-dsTrxR reduced <em>N. ceranae</em> numbers in the midgut and partially restored midgut morphology without affecting bee survival and gut microbial composition. The results of this study confirmed that liposomes could effectively protect dsRNA from entering the honeybee gut and provide a reference for using RNAi technology to suppress honeybee pests and diseases.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 853-860"},"PeriodicalIF":4.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001017/pdfft?md5=4766286501f4e15858133f504ab98853&pid=1-s2.0-S2405805X24001017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949676","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":"Comparative omics directed gene discovery and rewiring for normal temperature-adaptive red pigment synthesis by polar psychrotrophic fungus Geomyces sp. WNF-15A","authors":"Haoyu Long ,&nbsp;Jiawei Zhou ,&nbsp;Yanna Ren ,&nbsp;Jian Lu ,&nbsp;Nengfei Wang ,&nbsp;Haifeng Liu ,&nbsp;Xiangshan Zhou ,&nbsp;Menghao Cai","doi":"10.1016/j.synbio.2024.07.002","DOIUrl":"10.1016/j.synbio.2024.07.002","url":null,"abstract":"<div><p>The Antarctic fungus <em>Geomyces</em> sp. WNF-15A can produce high-quality red pigments (AGRP) with good prospects for the use in food and cosmetic area. However, efficient AGRP synthesis relies on low-temperature and thus limits its industrial development. Here genome sequencing and comparative analysis were performed on the wild-type versus to four mutants derived from natural mutagenesis and transposon insertion mutation. Eleven mutated genes were identified from 2309 SNPs and 256 Indels. A CRISPR-Cas9 gene-editing system was established for functional analysis of these genes. Deficiency of <em>scaffold1.t692</em> and <em>scaffold2.t704</em> with unknown functions highly improved AGRP synthesis at all tested temperatures. Of note, the two mutants produced comparable levels of AGRP at 20 °C to the wild-type at 14 °C. They also broke the normal-temperature limitation and effectively synthesized AGRP at 25 °C. Comparative metabolomic analysis revealed that deficiency of <em>scaffold1.t692</em> improved AGRP synthesis by regulation of global metabolic pathways especially downregulation of the competitive pathways. Knockout of key genes responsible for the differential metabolites confirmed the metabolomic results. This study shows new clues for cold-adaptive regulatory mechanism of polar fungi. It also provides references for exploitation and utilization of psychrotrophic fungal resources.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 842-852"},"PeriodicalIF":4.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001005/pdfft?md5=c8452042e6caff66b2f219f2a7e2a9af&pid=1-s2.0-S2405805X24001005-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732113","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":"Synergistic increase in coproporphyrin III biosynthesis by mitochondrial compartmentalization in engineered Saccharomyces cerevisiae","authors":"Qidi Guo ,&nbsp;Jiaqi Xu ,&nbsp;Jiacun Li ,&nbsp;Shuyan Tang ,&nbsp;Yuhui Cheng ,&nbsp;Bei Gao ,&nbsp;Liang-Bin Xiong ,&nbsp;Jie Xiong ,&nbsp;Feng-Qing Wang ,&nbsp;Dong-Zhi Wei","doi":"10.1016/j.synbio.2024.07.001","DOIUrl":"10.1016/j.synbio.2024.07.001","url":null,"abstract":"<div><p>Coproporphyrin III (CP III), a natural porphyrin derivative, has extensive applications in the biomedical and material industries. <em>S. cerevisiae</em> has previously been engineered to highly accumulate the CP III precursor 5-aminolevulinic acid (ALA) through the C4 pathway. In this study, a combination of cytoplasmic metabolic engineering and mitochondrial compartmentalization was used to enhance CP III production in <em>S. cerevisiae</em>. By integrating pathway genes into the chromosome, the CP III titer gradually increased to 32.5 ± 0.5 mg/L in shake flask cultivation. Nevertheless, increasing the copy number of pathway genes did not consistently enhance CP III synthesis. Hence, the partial synthesis pathway was compartmentalized in mitochondria to evaluate its effectiveness in increasing CP III production. Subsequently, by superimposing the mitochondrial compartmentalization strategy on cytoplasmic metabolic engineered strains, the CP III titer was increased to 64.3 ± 1.9 mg/L. Furthermore, augmenting antioxidant pathway genes to reduce reactive oxygen species (ROS) levels effectively improved the growth of engineered strains, resulting in a further increase in the CP III titer to 82.9 ± 1.4 mg/L. Fed-batch fermentations in a 5 L bioreactor achieved a titer of 402.8 ± 9.3 mg/L for CP III. This study provides a new perspective on engineered yeast for the microbial production of porphyrins.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 834-841"},"PeriodicalIF":4.4,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000991/pdfft?md5=5fa2900d55ebdd1243e8ea2c347b1c0f&pid=1-s2.0-S2405805X24000991-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141623980","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":"Cyanamide-inducible expression of homing nuclease I−SceI for selectable marker removal and promoter characterisation in Saccharomyces cerevisiae","authors":"Liam McDonnell ,&nbsp;Samuel Evans ,&nbsp;Zeyu Lu ,&nbsp;Mitch Suchoronczak ,&nbsp;Jonah Leighton ,&nbsp;Eugene Ordeniza ,&nbsp;Blake Ritchie ,&nbsp;Nik Valado ,&nbsp;Niamh Walsh ,&nbsp;James Antoney ,&nbsp;Chengqiang Wang ,&nbsp;Carlos Horacio Luna-Flores ,&nbsp;Colin Scott ,&nbsp;Robert Speight ,&nbsp;Claudia E. Vickers ,&nbsp;Bingyin Peng","doi":"10.1016/j.synbio.2024.06.009","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.009","url":null,"abstract":"<div><p>In synthetic biology, microbial chassis including yeast <em>Saccharomyces cerevisiae</em> are iteratively engineered with increasing complexity and scale. Wet-lab genetic engineering tools are developed and optimised to facilitate strain construction but are often incompatible with each other due to shared regulatory elements, such as the galactose-inducible (<em>GAL</em>) promoter in <em>S. cerevisiae</em>. Here, we prototyped the cyanamide-induced ^I−<em>Sce</em>I expression, which triggered double-strand DNA breaks (DSBs) for selectable marker removal. We further combined cyanamide-induced ^I−<em>Sce</em>I-mediated DSB and maltose-induced MazF-mediated negative selection for plasmid-free <em>in situ</em> promoter substitution, which simplified the molecular cloning procedure for promoter characterisation. We then characterised three tetracycline-inducible promoters showing differential strength, a non-leaky β-estradiol-inducible promoter, cyanamide-inducible <em>DDI2</em> promoter, bidirectional <em>MAL32/MAL31</em> promoters, and five pairs of bidirectional <em>GAL1/GAL10</em> promoters. Overall, alternative regulatory controls for genome engineering tools can be developed to facilitate genomic engineering for synthetic biology and metabolic engineering applications.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 820-827"},"PeriodicalIF":4.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X2400098X/pdfft?md5=a13d7248a6edd9e6adb4e09b95a48e69&pid=1-s2.0-S2405805X2400098X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542947","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":"Advances in stress-tolerance elements for microbial cell factories","authors":"Zheyi Kuang ,&nbsp;Xiaofang Yan ,&nbsp;Yanfei Yuan ,&nbsp;Ruiqi Wang ,&nbsp;Haifan Zhu ,&nbsp;Youyang Wang ,&nbsp;Jianfeng Li ,&nbsp;Jianwen Ye ,&nbsp;Haitao Yue ,&nbsp;Xiaofeng Yang","doi":"10.1016/j.synbio.2024.06.008","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.008","url":null,"abstract":"<div><p>Microorganisms, particularly extremophiles, have evolved multiple adaptation mechanisms to address diverse stress conditions during survival in unique environments. Their responses to environmental coercion decide not only survival in severe conditions but are also an essential factor determining bioproduction performance. The design of robust cell factories should take the balance of their growing and bioproduction into account. Thus, mining and redesigning stress-tolerance elements to optimize the performance of cell factories under various extreme conditions is necessary. Here, we reviewed several stress-tolerance elements, including acid-tolerant elements, saline-alkali-resistant elements, thermotolerant elements, antioxidant elements, and so on, providing potential materials for the construction of cell factories and the development of synthetic biology. Strategies for mining and redesigning stress-tolerance elements were also discussed. Moreover, several applications of stress-tolerance elements were provided, and perspectives and discussions for potential strategies for screening stress-tolerance elements were made.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 793-808"},"PeriodicalIF":4.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000978/pdfft?md5=9e21dff9414b79f288247d1c2878f9d9&pid=1-s2.0-S2405805X24000978-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542945","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":"Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa","authors":"Li Cao,&nbsp;Yangchun Liu,&nbsp;Lin Sun,&nbsp;Zirong Zhu,&nbsp;Danlu Yang,&nbsp;Ziyuan Xia,&nbsp;Duo Jin,&nbsp;Zirui Dai,&nbsp;Jie Rang,&nbsp;Liqiu Xia","doi":"10.1016/j.synbio.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.007","url":null,"abstract":"<div><p>Triacylglycerol (TAG) is crucial for antibiotic biosynthesis derived from <em>Streptomyces</em>, as it serves as an important carbon source. In this study, the supplementation of exogenous TAG led to a 3.92-fold augmentation in spinosad production. The impact of exogenous TAG on the metabolic network of <em>Saccharopolyspora spinosa</em> were deeply analyzed through comparative proteomics. To optimize TAG metabolism and enhance spinosad biosynthesis, the lipase-encoding genes <em>lip</em>886 and <em>lip</em>385 were overexpressed or co-expressed. The results shown that the yield of spinosad was increased by 0.8-fold and 0.4-fold when <em>lip</em>886 and <em>lip</em>385 genes were overexpressed, respectively. Synergistic co-expression of these genes resulted in a 2.29-fold increase in the yield of spinosad. Remarkably, the combined overexpression of <em>lip</em>886 and <em>lip</em>385 in the presence of exogenous TAG elevated spinosad yields by 5.5-fold, led to a drastic increase in spinosad production from 0.036 g/L to 0.234 g/L. This study underscores the modification of intracellular concentrations of free fatty acids (FFAs), short-chain acyl-CoAs, ATP, and NADPH as mechanisms by which exogenous TAG modulates spinosad biosynthesis. Overall, the findings validate the enhancement of TAG catabolism as a beneficial strategy for optimizing spinosad production and provide foundational insights for engineering secondary metabolite biosynthesis pathways in another <em>Streptomyces</em>.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 809-819"},"PeriodicalIF":4.4,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000966/pdfft?md5=c7e671fa9dfff8518fbfe866dcecef77&pid=1-s2.0-S2405805X24000966-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542946","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}