Recent advances of natural product pesticide milbemycins from Streptomyces DOI Creative Commons
Xue Yang,

Guozhong Du,

Xiaojin Li

et al.

New plant protection., Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Abstract Milbemycins are a group of 16‐membered macrolides produced by the soil‐dwelling filamentous bacteria Streptomyces . Renowned for their potent acaricidal and insecticidal properties, combined with low toxicity, milbemycins recognized as eco‐friendly biopesticides, vital pest control sustainable agricultural development. Over several decades, have been extensively investigated, achieving significant progress, including advancements in biological activities (such mechanisms toxicity studies), biosynthetic regulatory mechanisms, high‐yield strain engineering strategies, development milbemycin‐derived commercial products applications. This review discusses recent advances, current limitations, ongoing emerging efforts to overcome limitations milbemycin research. Finally, future research directions outlined superior milbemycin‐producing cell factories facilitate widespread application field.

Language: Английский

Improving polyketide biosynthesis by rescuing the translation of truncated mRNAs into functional polyketide synthase subunits DOI Creative Commons
Yan Liu,

Chaoyi Song,

Qingwen Cui

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 17, 2025

Language: Английский

Citations

0

Overproduction of endusamycin in Streptomyces endus subsp. aureus DOI Creative Commons

Yingying Chang,

Zhen Liu,

Zixin Deng

et al.

Synthetic and Systems Biotechnology, Journal Year: 2025, Volume and Issue: 10(2), P. 523 - 531

Published: Feb. 14, 2025

Endusamycin, a naturally occurring polyether ionophore antibiotic, exhibits extensive antitumor activities. Despite its promising potential, the titer of endusamycin is significantly lower compared to widely used compounds, and no reports have been published regarding overproduction. In this study, various metabolic engineering strategies were performed enhance production. Notably, deletion competing biosynthetic gene clusters (BGCs) responsible for biosynthesis spore pigment meilingmycin-like compounds based on transcriptome analysis, as well doubling BGC, proved be effective. These interventions resulted in 20 % 69 increase endusamycin, respectively. Furthermore, systematic optimization fermentation medium components, including carbon source, nitrogen phosphorus potassium, contributed further endusamycin. Ultimately, high-yielding strain YC1109 was developed through integration these strategies. The reached 5469 mg/L shake-flask 5011 fed-batch fermentation, representing 246 original strain. This research facilitates drug development industrialization It establishes superior chassis exploring derivatives provides valuable insights into improving production compounds.

Language: Английский

Citations

0

Dynamic regulation combined with systematic metabolic engineering for high-level palmitoleic acid accumulation in oleaginous yeast DOI
Yufan Zhou,

Mei-Li Sun,

Lu Lin

et al.

Metabolic Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0

CRISPRi-mediated multigene downregulating redirects the metabolic flux to spinosad biosynthesis in Saccharopolyspora spinosa DOI Creative Commons

Zirong Zhu,

Li Cao,

Ziyuan Xia

et al.

Synthetic and Systems Biotechnology, Journal Year: 2025, Volume and Issue: 10(2), P. 583 - 592

Published: Feb. 20, 2025

Microorganisms are often likened to complex production workshops. In Saccharopolyspora spinosa (S. spinosa), the biosynthesis of spinosad is a line within its intricate workshop. Optimizing entire environment and reducing unnecessary metabolic flow essential increasing yield. Pyruvate serves as crucial precursor for biosynthesis. Previous studies revealed that pyc gene highly expressed in gluconeogenic pathway, leading pyruvate shunt. By downregulating pyc, we enhanced yield, although improvement was below expectations. We speculated most accumulated following knockdown entered some synthetic pathways unrelated spinosad. Through pathway qRT-PCR analyses, found expression levels gltA1 atoB3 tributary, including TCA cycle ethylmalonyl-CoA were significantly increased strain. The combined these three genes optimized line, yield 633.1 ± 38.6 mg/L, representing 199.4 % increase. This study identifies key optimizing offers insights into screening efficient construction Spinosad-producing strains.

Language: Английский

Citations

0

Hybrid Biological-Chemical Strategy for Converting Polyethylene into a Recyclable Plastic Monomer Using Engineered Corynebacterium glutamicum DOI
Chunjun Zhan, Guangxu Lan, Qingyun Dan

et al.

Metabolic Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0

High-Level De Novo Production of (2S)-Naringenin in Yarrowia lipolytica Using Metabolic and Enzyme Engineering DOI

Ziyun Ru,

Mengsu Liu,

Qihang Chen

et al.

ACS Agricultural Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Language: Английский

Citations

0

Metabolic Engineering of Escherichia coli for the Improved Malonic Acid Production DOI
Han Liu,

Mengzhen Tian,

Pingsha Dong

et al.

ACS Synthetic Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Malonic acid (MA) is a high-value chemical with diverse applications in the fields of food, agriculture, medicine, and synthesis. Despite successful biosynthesis MA has been performed Escherichia coli, Myceliophthora thermophila, Saccharomyces cerevisiae, resulting titers remain insufficient for industrial-scale production. In this study, three distinct metabolic pathways were designed constructed to increase production E. coli. Among these, fumaric pathway comprising four key enzymes including aspartase (AspA), decarboxylase (PanD), β-alanine-pyruvate transaminase (Pa0132), succinic aldehyde dehydrogenase (YneI) was identified as most effective Additionally, supplementation found significantly improve To further enhance production, engineering strategies employed, deletion ydfG gene, responsible encoding malonic semialdehyde reductase, ptsG which encodes glucose transporter. Finally, through optimization fermentation conditions feeding strategies, engineered strain achieved an titer 1.4 g/L shake flask 17.8 fed-batch fermentation. This study provides new insights into utilizing metabolically coli cells.

Language: Английский

Citations

0

Improving Precursor Supply and Optimizing the Fermentation Process for High-Level Production of Docosapentaenoic Acid in Yarrowia Lipolytica DOI
Fei Du,

Y. O. HANG,

Feng Zhang

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Docosapentaenoic acid (DPA) is widely applied in medicine and health products because of its important physiological functions. Using microbial cell factories for DPA production considered a viable alternative to extracting from seal oil. In this study, an engineering strategy the efficient was developed. First, biosynthesis pathway successfully established Yarrowia lipolytica. Then, increase acetyl-CoA by citrate metabolism malonyl-CoA introducing new orthogonal synthesis further enhance production. Furthermore, overexpression glucose-6-phosphate dehydrogenase (G6PDH) malic enzyme (ME) enhanced NADPH availability. Finally, optimizing fermentation conditions, content engineered strain reached 40.0%, yield 13.0 g/L 5 L bioreactor, representing highest levels reported so far Y. This study provides promising construct fatty biosynthesis.

Language: Английский

Citations

0

Enhanced biosynthesis of poly(3‐hydroxybutyrate) in engineered strains of Pseudomonas putidavia increased malonyl‐CoA availability DOI Creative Commons
Giusi Favoino, Nicolas Krink, Tobias Schwanemann

et al.

Microbial Biotechnology, Journal Year: 2024, Volume and Issue: 17(11)

Published: Nov. 1, 2024

Abstract Malonyl‐coenzyme A (CoA) is a key precursor for the biosynthesis of multiple value‐added compounds by microbial cell factories, including polyketides, carboxylic acids, biofuels, and polyhydroxyalkanoates. Owing to its role as metabolic hub, malonyl‐CoA availability limited competition in several essential pathways. To address this limitation, we modified genome‐reduced Pseudomonas putida strain increase acetyl‐CoA carboxylation while limiting utilization. Genes involved sugar catabolism regulation, tricarboxylic acid (TCA) cycle, fatty were knocked‐out specific combinations towards increasing pool. An enzyme‐coupled biosensor, based on rppA gene, was employed monitor levels vivo. RppA type III polyketide synthase that converts into flaviolin, red‐colored polyketide. We isolated strains displaying enhanced via colorimetric screening method RppA‐dependent red pigmentation; direct flaviolin quantification identified four engineered had significant levels. further these adding non‐canonical pathway uses poly(3‐hydroxybutyrate) biosynthesis. These manipulations led increased polymer accumulation fully strains, validating our general strategy boost output malonyl‐CoA–dependent pathways P .

Language: Английский

Citations

3

Effect of Precursors and Their Regulators on the Biosynthesis of Antibiotics in Actinomycetes DOI Creative Commons

Xu Yan,

Yao Dong,

Yawen Gu

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 1132 - 1132

Published: March 3, 2024

During the life activities of microorganisms, a variety secondary metabolites are produced, including antimicrobials and antitumor drugs, which widely used in clinical practice. In addition to exploring new antibiotics, this makes it one research priorities Actinomycetes effectively increase yield antibiotics production strains by various means. Most antibiotic-producing have functional regulatory factors that regulate their growth, development, metabolite biosynthesis processes. Through study precursor substances antibiotic biosynthesis, researchers revealed process mechanism synthesis regulators affect metabolites, can be obtain engineered with high production. This paper summarizes supply precursors progress on role biosynthesis. lays foundation for establishment effective breeding methods improve yields through manipulation genes related regulators.

Language: Английский

Citations

2