Fig. 2: BioPKS pipeline combinatorially designs novel, chimeric PKSs from existing PKSs to produce intermediates structurally similar to the target molecule. | Nature Communications

Fig. 2: BioPKS pipeline combinatorially designs novel, chimeric PKSs from existing PKSs to produce intermediates structurally similar to the target molecule.

From: Merging the computational design of chimeric type I polyketide synthases with enzymatic pathways for chemical biosynthesis

Fig. 2

When a target molecule is input, BioPKS pipeline first calls upon RetroTide to suggest chimeric PKS designs by combinatorially mixing domains from existing PKSs, such as rapamycin synthase or 6-deoxyerythronolide B synthase (DEBS). Here, each color represents a domain from a distinct known PKS. RetroTide’s PKS designs are output in descending order of chemical similarity as measured between the corresponding PKS product and the target chemical. If the target can be synthesized solely with PKSs, BioPKS pipeline stops, and users can search the ClusterCAD 2.0 database for closely matched PKSs. If the target cannot be synthesized by PKSs, then BioPKS pipeline calls upon DORAnet to modify the top-ranked PKS product with monofunctional enzymes, whose activities are digitally encoded as reaction rules. The post-PKS pathways generated can then be ranked with thermodynamics and/or pathway feasibility analyses. If the top-ranked PKS product does not lead to the final target through post-PKS modifications, then alternate PKS designs are considered.

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