SBSPKS

SBSPKS performs sequence- and structure-based analysis of modular Type I polyketide synthases (PKSs) to support genome mining and biosynthetic engineering of polyketide secondary metabolites.

Key Features:

• Model_3D_PKS: Models three-dimensional structures of individual PKS catalytic domains, constructs dimeric structures for complete PKS modules, and predicts substrate specificity.
• Dock_Dom_Anal: Identifies interacting residue pairs at inter-subunit interfaces by aligning inter-polypeptide linker sequences with docking domain structures and predicts cognate order of substrate channeling in modular PKS systems with multiple open reading frames (ORFs) via combinatorial evaluation of interface contacts.
• NRPS-PKS: Identifies catalytic domains within Type I PKS protein sequences and compares them with experimentally characterized PKS/NRPS clusters cataloged in SBSPKS backend databases for functional annotation and comparative analysis.

Scientific Applications:

• Natural product discovery: Facilitates genome mining to identify novel polyketide biosynthetic gene clusters and candidate PKSs for secondary metabolite discovery.
• Biosynthetic engineering: Guides rational design of novel secondary metabolites by providing substrate specificity predictions and structural models of PKS domains and modules.
• Structural-functional studies: Supports interpretation of PKS mechanism by leveraging crystal structures of PKS catalytic and docking domains and mammalian fatty acid synthase modules.

Methodology:

Structural bioinformatics modeling of 3D PKS catalytic and docking domains, sequence alignment of inter-polypeptide linker sequences with docking domain structures to identify interacting residue pairs and predict substrate specificity, and combinatorial evaluation of all possible interface contacts to predict cognate substrate-channeling order.