Ribosome engineering of Myxococcus xanthus for enhancing the heterologous production of epothilones DOI Creative Commons
Kang Xu,

Xiao-ran Yue,

C.M. Wang

и другие.

Microbial Cell Factories, Год журнала: 2024, Номер 23(1)

Опубликована: Дек. 27, 2024

Ribosome engineering is a semi-empirical technique used to select antibiotic-resistant mutants that exhibit altered secondary metabolism. This method has been demonstrated effectively with enhanced synthesis of natural products in many bacterial species, including actinomycetes. Myxobacteria are recognized as fascinating producers active products. However, it remains uncertain whether this similarly effective myxobacteria, especially for the heterologous production epothilones Myxococcus xanthus. Antibiotics target ribosome and RNA polymerase (RNAP) were evaluated epothilone-producing strain M. xanthus ZE9. The epothilone was dramatically different resistant mutants. We screened neomycin rifampicin found yield mutant ZE9N-R22 improved by sixfold compared Our findings indicate growth mutants, upregulation biosynthetic genes, specific mutations identified through genome re-sequencing may collectively contribute improvement. Ultimately, total titer achieved 10 L bioreactor reached 93.4 mg/L. an efficient approach obtain strains various interference mechanisms. Here, we discuss potential mechanisms method.

Язык: Английский

Natural sideromycins and siderophore-conjugated natural products as inspiration for novel antimicrobial agents DOI

Zhiying Miao,

Jing Lin, Wei‐Min Chen

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 117333 - 117333

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Whole-cell biocatalysis with Myxococcus xanthus DOI
Lea Winand, Markus Nett

Methods in enzymology on CD-ROM/Methods in enzymology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Design, synthesis, molecular docking and ADME of novel phenylalanine derivatives as mushroom tyrosinase inhibitors DOI

Longhao Wang,

Shunshun Lei,

Liyun Du

и другие.

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2025, Номер unknown, С. 130211 - 130211

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
An upgraded Myxococcus xanthus chassis with enhanced growth characteristics for efficient genetic manipulation DOI Creative Commons
Wei-feng Hu,

Yan Wang,

Xiao-ran Yue

и другие.

Engineering Microbiology, Год журнала: 2024, Номер 4(3), С. 100155 - 100155

Опубликована: Июнь 4, 2024

Myxobacteria are well known for multicellular social behaviors and valued biosynthesis of natural products. such as clumping growth severely hamper strain cultivation genetic manipulation. Using Myxococcus xanthus DK1622, we engineered Hu04, which is deficient in behavior pigmentation. while maintaining nutritional a similar metabolic background, exhibits improved dispersed growth, streamlining operational procedures. It achieves high cell densities culture promising synthetic biology applications.

Язык: Английский

Процитировано

1
MyxoPortal: a database of myxobacterial genomic features DOI Creative Commons

Rayapadi G Swetha,

Benita S Arakal,

Santhosh Rajendran

и другие.

Database, Год журнала: 2024, Номер 2024

Опубликована: Янв. 1, 2024

Abstract Myxobacteria are predatory bacteria with antimicrobial activity, utilizing complex mechanisms to kill their prey and assimilate macromolecules. Having large genomes encoding hundreds of secondary metabolites, hydrolytic enzymes peptides, these organisms widely studied for antibiotic potential. MyxoPortal is a comprehensive genomic database hosting 262 myxobacterial strains. Datasets included provide genome annotations gene locations, functions, amino acids nucleotide sequences, allowing analysis evolutionary taxonomical relationships between strains genes. Biosynthetic clusters identified by AntiSMASH, dbAMP-generated peptide sequences as resource novel discoveries, while curated datasets CRISPR/Cas genes, regulatory protein phage associated genes give useful insights into each strain’s biological properties. an intuitive open-source that brings together application-oriented features can be used in taxonomy, evolution, predation research. accessed at http://dicsoft1.physics.iisc.ac.in/MyxoPortal/. Database URL: Graphical

Язык: Английский

Процитировано

1
Combining culture optimization and synthetic biology to improve production and detection of secondary metabolites in Myxococcus xanthus : application to myxoprincomide DOI Creative Commons

Mathieu Sourice,

Charlotte Simmler, Marc Maresca

и другие.

Microbiology Spectrum, Год журнала: 2024, Номер 12(12)

Опубликована: Окт. 21, 2024

ABSTRACT Microbial secondary metabolites play crucial ecological roles in governing species interactions and contributing to their defense strategies. Their unique structures potent bioactivities have been key discovering antibiotics anticancer drugs. Genome sequencing has undoubtedly revealed that myxobacteria constitute a huge reservoir of as the well-known producers, actinomycetes. However, because most are not produced laboratory context, natural products from characterized date represent only tip iceberg. By combining engineering dedicated Myxococcus xanthus DZ2 chassis strain with two-step growth medium protocol, we provide new approach called Protocol for Resource Integration Maximization–Biomolecules Overproduction Optimal Screening Therapeutics (2PRIM-BOOST) production non-ribosomal peptides synthetases (NRPS)/polyketides synthases (PKS) myxobacteria. We further show 2PRIM-BOOST strategy will facilitate screening biological activities medical interest. As proof concept, using constitutive strong promoter, myxoprincomide M. efficiently its biosynthesis enhanced approach, allowing identification features myxoprincomide. This should allow chances produce discover NRPS, PKS, mixed NRPS/PKS hybrid currently considered cryptic represented IMPORTANCE important also prolific source Myxobacteria ubiquitous soil-dwelling bacteria constituting metabolites. these molecules one can estimate one-tenth date. Here, developed combines together optimization. strategies insertion promoter upstream biosynthetic gene cluster (BGC), myxoprincomide, low-produced metabolite, was successfully significantly increased. The enriches toolbox used previously metabolites, unveil role,

Язык: Английский

Процитировано

1
Harnessing Gram‐negative bacteria for novel anti‐Gram‐negative antibiotics DOI Creative Commons
Joy Birkelbach, Carsten E. Seyfert, Sebastian Walesch

и другие.

Microbial Biotechnology, Год журнала: 2024, Номер 17(11)

Опубликована: Ноя. 1, 2024

Abstract Natural products have proven themselves as a valuable resource for antibiotics. However, in view of increasing antimicrobial resistance, there is an urgent need new, structurally diverse agents that the potential to overcome resistance and treat Gram‐negative pathogens particular. Historically, search new antibiotics was strongly focussed on very successful Actinobacteria. On other hand, producer strains been under‐sampled their production bioactive natural has underestimated. In this mini‐review, we highlight prominent examples novel anti‐Gram negative produced by bacteria are currently lead optimisation or preclinical development. Furthermore, will provide insights into considerations strategies behind discovery these putative applications.

Язык: Английский

Процитировано

1
Ribosome engineering of Myxococcus xanthus for enhancing the heterologous production of epothilones DOI Creative Commons
Kang Xu,

Xiao-ran Yue,

C.M. Wang

и другие.

Microbial Cell Factories, Год журнала: 2024, Номер 23(1)

Опубликована: Дек. 27, 2024

Ribosome engineering is a semi-empirical technique used to select antibiotic-resistant mutants that exhibit altered secondary metabolism. This method has been demonstrated effectively with enhanced synthesis of natural products in many bacterial species, including actinomycetes. Myxobacteria are recognized as fascinating producers active products. However, it remains uncertain whether this similarly effective myxobacteria, especially for the heterologous production epothilones Myxococcus xanthus. Antibiotics target ribosome and RNA polymerase (RNAP) were evaluated epothilone-producing strain M. xanthus ZE9. The epothilone was dramatically different resistant mutants. We screened neomycin rifampicin found yield mutant ZE9N-R22 improved by sixfold compared Our findings indicate growth mutants, upregulation biosynthetic genes, specific mutations identified through genome re-sequencing may collectively contribute improvement. Ultimately, total titer achieved 10 L bioreactor reached 93.4 mg/L. an efficient approach obtain strains various interference mechanisms. Here, we discuss potential mechanisms method.

Язык: Английский

Процитировано

1