Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

A hybrid modular polyketide synthase obtained by domain swapping

M Oliynyk1, M J Brown, J Cortés

  • 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. pfl10@mole.bio.cam.ac.uk

Chemistry & Biology
|October 1, 1996
PubMed
Summary

Researchers created a hybrid enzyme by swapping an acyltransferase (AT) domain in a modular polyketide synthase. This modification yielded novel triketide lactones, demonstrating domain swapping for altered antibiotic synthesis.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Analysis of UGT1A1 germline variants in patients with advanced breast cancer treated with trastuzumab-deruxtecan: results from the PROCURE Project.

ESMO open·2026
Same author

A chemotherapy-free, pathological response-adapted strategy using trastuzumab-pertuzumab and T-DM1 in HER2-positive early breast cancer: the PHERGain-2 study.

Annals of oncology : official journal of the European Society for Medical Oncology·2026
Same author

The emerging role of the microbiome in bladder cancer: prognostic implications and treatment response.

Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas·2026
Same author

Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial.

Annals of oncology : official journal of the European Society for Medical Oncology·2026
Same author

Sacituzumab govitecan in patients with metastatic breast cancer: pooled safety analysis of data from patients in North America, Europe, and Asia.

ESMO open·2026
Same author

Human epidermal growth factor receptor 2 (HER2) expression dynamics between diagnosis and recurrence in patients with breast cancer using artificial intelligence and electronic health records: the RosHER study.

ESMO real world data and digital oncology·2026

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Synthetic Biology

Background:

  • Modular polyketide synthases (PKS) are crucial for synthesizing medically important antibiotics.
  • Understanding genetic manipulation of PKS is key to developing novel polyketide compounds.
  • The DEBS1-TE model system, derived from the erythromycin PKS, was used for analysis.

Purpose of the Study:

  • To determine if individual domains within a PKS can be replaced by homologous domains from other PKS.
  • To create a functional hybrid enzyme through domain swapping.
  • To investigate the impact of acyltransferase (AT) domain replacement on product specificity.

Main Methods:

  • Utilized the DEBS1-TE model system, comprising the first two modules of the Saccharopolyspora erythraea erythromycin PKS.

Related Experiment Videos

  • Replaced the AT domain of module 1 in DEBS1-TE with the AT domain from module 2 of the rapamycin PKS.
  • Analyzed the resulting hybrid enzyme's product profile.

    • Main Results:

    • The hybrid enzyme successfully synthesized two novel triketide lactones, replacing the original products.
    • The novel lactones lacked a methyl group at the C-4 position of the lactone ring.
    • The AT domain swap resulted in a functional hybrid enzyme with altered chain extension specificity.

    Conclusions:

    • Demonstrated that a core structural domain (AT) of a modular PKS can be swapped to create functional hybrid enzymes.
    • This approach allows for rational alteration of chain extension specificity in PKS.
    • Suggests potential for generating novel antibiotic analogues inaccessible through traditional chemical synthesis and encourages further domain swapping experiments.