Synthetic and Systems Biotechnology最新文献

{"title":"Enhancing levan biosynthesis by destroying the strongly acidic environment caused by membrane-bound glucose dehydrogenase (mGDH) in Gluconobacter sp. MP2116","authors":"Junjie Tian ,&nbsp;Shumin Wei ,&nbsp;Wenxing Liang ,&nbsp;Guangyuan Wang","doi":"10.1016/j.synbio.2024.08.005","DOIUrl":"10.1016/j.synbio.2024.08.005","url":null,"abstract":"<div><p>Levan produced by <em>Gluconobacter</em> spp. has great potential in biotechnological applications. However, <em>Gluconobacter</em> spp. can synthesize organic acids during fermentation, resulting in environmental acidification. Few studies have focused on the effects of environmental acidification on levan synthesis. This study revealed that the organic acids, mainly gluconic acid (GA) and 2-keto-gluconic acid (2KGA) secreted by <em>Gluconobacter</em> sp. MP2116 created a highly acidic environment (pH &lt; 3) that inhibited levan biosynthesis. The levansucrase derived from strain MP2116 had high enzyme activity at pH 4.0 ∼ pH 6.5. When the ambient pH was less than 3, the enzyme activity decreased by 67 %. Knocking out the <em>mgdh</em> gene of membrane-bound glucose dehydrogenase (mGDH) in the GA and 2KGA synthesis pathway in strain MP2116 eliminated the inhibitory effect of high acid levels on levansucrase function. As a result, the levan yield increased from 7.4 g/l (wild-type) to 18.8 g/l (Δ<em>mgdh</em>) during fermentation without pH control. This study provides a new strategy for improving levan production by preventing the inhibition of polysaccharide synthesis by environmental acidification.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 68-75"},"PeriodicalIF":4.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001169/pdfft?md5=d2bc19bfe837c1f30763278c26cd8634&pid=1-s2.0-S2405805X24001169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142039739","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":"Systematic metabolic engineering enables highly efficient production of vitamin A in Saccharomyces cerevisiae","authors":"Yi Shi ,&nbsp;Shuhuan Lu ,&nbsp;Xiao Zhou ,&nbsp;Xinhui Wang ,&nbsp;Chenglong Zhang ,&nbsp;Nan Wu ,&nbsp;Tianyu Dong ,&nbsp;Shilong Xing ,&nbsp;Ying Wang ,&nbsp;Wenhai Xiao ,&nbsp;Mingdong Yao","doi":"10.1016/j.synbio.2024.08.004","DOIUrl":"10.1016/j.synbio.2024.08.004","url":null,"abstract":"<div><p>Vitamin A is a micronutrient critical for versatile biological functions and has been widely used in the food, cosmetics, pharmaceutical, and nutraceutical industries. Synthetic biology and metabolic engineering enable microbes, especially the model organism <em>Saccharomyces cerevisiae</em> (generally recognised as safe) to possess great potential for the production of vitamin A. Herein, we first generated a vitamin A-producing strain by mining β-carotene 15,15′-mono(di)oxygenase from different sources and identified two isoenzymes <em>Mbblh</em> and <em>Ssbco</em> with comparable catalytic properties but different catalytic mechanisms. Combinational expression of isoenzymes increased the flux from β-carotene to vitamin A metabolism. To modulate the vitamin A components, retinol dehydrogenase 12 from <em>Homo sapiens</em> was introduced to achieve more than 90 % retinol purity using shake flask fermentation. Overexpressing <em>POS5Δ17</em> enhanced the reduced nicotinamide adenine dinucleotide phosphate pool, and the titer of vitamin A was elevated by almost 46 %. Multi-copy integration of the key rate-limiting step gene <em>Mbblh</em> further improved the synthesis of vitamin A. Consequently, the titer of vitamin A in the strain harbouring the Ura3 marker was increased to 588 mg/L at the shake-flask level. Eventually, the highest reported titer of 5.21 g/L vitamin A in <em>S. cerevisiae</em> was achieved in a 1-L bioreactor. This study unlocked the potential of <em>S. cerevisiae</em> for synthesising vitamin A in a sustainable and economical way, laying the foundation for the commercial-scale production of bio-based vitamin A.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 58-67"},"PeriodicalIF":4.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001157/pdfft?md5=e084c2a4b3b96f9c53f2c9bc1be6d9ea&pid=1-s2.0-S2405805X24001157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012685","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":"Engineering artificial cross-species promoters with different transcriptional strengths","authors":"Wenjie Zuo ,&nbsp;Guobin Yin ,&nbsp;Luyao Zhang ,&nbsp;Weijiao Zhang ,&nbsp;Ruirui Xu ,&nbsp;Yang Wang ,&nbsp;Jianghua Li ,&nbsp;Zhen Kang","doi":"10.1016/j.synbio.2024.08.003","DOIUrl":"10.1016/j.synbio.2024.08.003","url":null,"abstract":"<div><p>As a fundamental tool in synthetic biology, promoters are pivotal in regulating gene expression, enabling precise genetic control and spurring innovation across diverse biotechnological applications. However, most advances in engineered genetic systems rely on host-specific regulation of the genetic portion. With the burgeoning diversity of synthetic biology chassis cells, there emerges a pressing necessity to broaden the universal promoter toolkit spectrum, ensuring adaptability across various microbial chassis cells for enhanced applicability and customization in the evolving landscape of synthetic biology. In this study, we analyzed and validated the primary structures of natural endogenous promoters from <em>Escherichia coli</em>, <em>Bacillus subtilis</em>, <em>Corynebacterium glutamicum</em>, <em>Saccharomyces cerevisiae</em>, and <em>Pichia pastoris</em>, and through strategic integration and rational modification of promoter motifs, we developed a series of cross-species promoters (P_sh) with transcriptional activity in five strains (prokaryotic and eukaryotic). This series of cross species promoters can significantly expand the synthetic biology promoter toolkit while providing a foundation and inspiration for standardized development of universal components The combinatorial use of key elements from prokaryotic and eukaryotic promoters presented in this study represents a novel strategy that may offer new insights and methods for future advancements in promoter engineering.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 49-57"},"PeriodicalIF":4.4,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001145/pdfft?md5=0d60323195a11533b64443b42b3f90d5&pid=1-s2.0-S2405805X24001145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141953883","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":"Establishment of the CRISPR-Cpf1 gene editing system in Bacillus licheniformis and multiplexed gene knockout","authors":"Suxin Liu ,&nbsp;Fengxu Xiao ,&nbsp;Youran Li ,&nbsp;Yupeng Zhang ,&nbsp;Yanling Wang ,&nbsp;Guiyang Shi","doi":"10.1016/j.synbio.2024.08.002","DOIUrl":"10.1016/j.synbio.2024.08.002","url":null,"abstract":"<div><p><em>Bacillus licheniformis</em> is a significant industrial microorganism. Traditional gene editing techniques relying on homologous recombination often exhibit low efficiency due to their reliance on resistance genes. Additionally, the established CRISPR gene editing technology, utilizing Cas9 endonuclease, faces challenges in achieving simultaneous knockout of multiple genes. To address this limitation, the CRISPR-Cpf1 system has been developed, enabling multiplexed gene editing across various microorganisms. Key to the efficient gene editing capability of this system is the rigorous screening of highly effective expression elements to achieve conditional expression of protein Cpf1. In this study, we employed mCherry as a reporter gene and harnessed P_<em>mal</em> for regulating the expression of Cpf1 to establish the CRISPR-Cpf1 gene editing system in <em>Bacillus licheniformis</em>. Our system achieved a 100 % knockout efficiency for the single gene <em>vpr</em> and up to 80 % for simultaneous knockout of the double genes <em>epr</em> and <em>mpr</em>. Furthermore, the culture of a series of protease-deficient strains revealed that the protease encoded by <em>aprE</em> contributed significantly to extracellular enzyme activity (approximately 80 %), whereas proteases encoded by <em>vpr</em>, <em>epr</em>, and <em>mpr</em> genes contributed to a smaller proportion of extracellular enzyme activity. These findings provide support for effective molecular modification and metabolic regulation in industrial organisms.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 39-48"},"PeriodicalIF":4.4,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001133/pdfft?md5=f69f2f7760a9aa1a358ca6c2a316639b&pid=1-s2.0-S2405805X24001133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141964151","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":"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}