ClusterCAD

ClusterCAD enables exploration and engineering of type I modular polyketide synthases (PKSs), PKS‑NRPS hybrid clusters, and nonribosomal peptide synthetases (NRPSs) by providing a curated database and analytical resources to support systematic combinatorial biosynthesis of novel natural products.

Key Features:

• Curated cluster database: An extensively curated collection of PKS, PKS‑NRPS hybrid, and NRPS gene clusters is provided for sequence- and domain-level analysis.
• Support for PKS‑NRPS hybrids and NRPSs: Explicit inclusion and support for PKS‑NRPS hybrid clusters and standalone NRPS clusters expands the range of megasynthase systems available for study.
• Chemical starters and loading modules: A diverse set of chemical starters and loading modules is included to inform biosynthetic initiation and combinatorial design.
• Domain Architecture Cluster Search Tool: A search and analysis capability for identifying and examining domain arrangements within clusters aids investigation of domain organization.
• Offline Jupyter Notebook workspace: A local Jupyter Notebook workspace is available for performing analyses and design workflows outside of an online session.
• Support for engineered PKS variant design: Resources and data aimed at designing and testing engineered PKS variants facilitate systematic combinatorial biosynthesis efforts.

Scientific Applications:

• Novel natural product generation: Systematic combinatorial biosynthesis of novel chemicals for applications including pharmaceuticals, biomaterials, and biofuels.
• Engineered enzyme design and testing: Design and evaluation of engineered PKS and PKS‑NRPS variants to alter product structures.
• Domain architecture analysis: Investigation of domain arrangements to inform understanding of fold and function determinants in PKS and NRPS systems.
• Expansion of accessible chemical space: Use of hybrid clusters and diverse starters/loading modules to explore broader biosynthetic product diversity.

Methodology:

Curated database assembly of PKS, PKS‑NRPS hybrid, and NRPS clusters; Domain Architecture Cluster Search Tool for identification and analysis of domain arrangements; provision of an offline Jupyter Notebook workspace for conducting analyses.