High-resolution structural analysis of native amphotericin megasynthases
NCCIH - National Center for Complementary and Integrative Health
About This Grant
Project Summary. Polyketide natural products have provided critical therapeutics, and they will remain an important component of new drug discovery and manufacturing. This program aims to develop new technologies to enable the high resolution cryo-EM structural elucidation of Type I polyketide synthases (PKSs) isolated directly from natural producer organisms. To date these megasynthase proteins have proven challenging for structural biology studies due to significant technical challenges, including extremely large molecular weights, difficult heterologous expression and highly dynamic structural features. As such, very few structures have been reported, and most are at low resolution and do not represent full synthases. We have recently developed tools for dual site-selective crosslinking of PKSs that enforces dynamic constraint and has led to the collection of high- resolution cryo-EM structures in single-modular Type I PKSs. Here we propose the development of two key tools. The first will convert native holo-PKSs to their cognate apo- forms to enable crosslinking within native PKSs. The second is the development protein isolation methodologies for very large megasynthases (500 kDa to 2 MDa) from within native producer proteomes, such that the resulting isolated forms can be structurally elucidated by cryo-EM. The amphotericin synthase pathway from producer bacterium Streptomyces nodosus will serve as a model system for high-resolution structural analysis. Together these tools will offer a fundamental step-change in access to molecular detail of PKS megasynthase structure.
Grant Summary
High-resolution structural analysis of native amphotericin megasynthases is a NCCIH - National Center for Complementary and Integrative Health grant providing up to $440K for university, nonprofit, healthcare org. Applications are due 2028-03-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $440K
2028-03-31
- 1Confirm your organization is eligible for High-resolution structural analysis of native amphotericin megasynthases from NCCIH - National Center for Complementary and Integrative Health, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCCIH - National Center for Complementary and Integrative Health before the deadline.
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High-resolution structural analysis of native amphotericin megasynthases: Frequently Asked Questions
Who is eligible for the High-resolution structural analysis of native amphotericin megasynthases?
High-resolution structural analysis of native amphotericin megasynthases is offered by NCCIH - National Center for Complementary and Integrative Health and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the High-resolution structural analysis of native amphotericin megasynthases provide?
High-resolution structural analysis of native amphotericin megasynthases provides up to $440K per award from NCCIH - National Center for Complementary and Integrative Health. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the High-resolution structural analysis of native amphotericin megasynthases deadline?
Applications for High-resolution structural analysis of native amphotericin megasynthases are due 2028-03-31 (open). Because deadlines can change, verify the date with the funder, NCCIH - National Center for Complementary and Integrative Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the High-resolution structural analysis of native amphotericin megasynthases?
To apply for High-resolution structural analysis of native amphotericin megasynthases, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCCIH - National Center for Complementary and Integrative Health.