ClusterCAD: a computational platform for type I modular polyketide synthase design

Eng, Clara H.; Backman, Tyler W H; Bailey, Constance B.; Magnan, Christophe; Garcia Martin, Hector; Katz, Leonard; Baldi, Pierre; Keasling, Jay D.

doi:10.1093/nar/gkx893

ClusterCAD: a computational platform for type I modular polyketide synthase design

Journal Article · Wed Oct 11 00:00:00 EDT 2017 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkx893· OSTI ID:1433111

Eng, Clara H. ^[1]; Backman, Tyler W H ^[2]; Bailey, Constance B. ^[3]; Magnan, Christophe ^[4]; Garcia Martin, Hector ^[2]; Katz, Leonard ^[5]; Baldi, Pierre ^[4]; Keasling, Jay D. ^[6]

Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Agile BioFoundry, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
Univ. of California, Irvine, CA (United States). Dept. of Computer Science and Inst. for Genomics and Bioinformatics
Univ. of California, Berkeley, CA (United States). QB3 Inst.
Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering and QB3 Inst. and Dept. of Bioengineering; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Agile BioFoundry, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Technical Univ. of Denmark, Horsholm (Denmark). Novo Nordisk Foundation Center for Biosustainability

Here, we present ClusterCAD, a web-based toolkit designed to leverage the collinear structure and deterministic logic of type I modular polyketide synthases (PKSs) for synthetic biology applications. The unique organization of these megasynthases, combined with the diversity of their catalytic domain building blocks, has fueled an interest in harnessing the biosynthetic potential of PKSs for the microbial production of both novel natural product analogs and industrially relevant small molecules. However, a limited theoretical understanding of the determinants of PKS fold and function poses a substantial barrier to the design of active variants, and identifying strategies to reliably construct functional PKS chimeras remains an active area of research. In this work, we formalize a paradigm for the design of PKS chimeras and introduce ClusterCAD as a computational platform to streamline and simplify the process of designing experiments to test strategies for engineering PKS variants. ClusterCAD provides chemical structures with stereochemistry for the intermediates generated by each PKS module, as well as sequence- and structure-based search tools that allow users to identify modules based either on amino acid sequence or on the chemical structure of the cognate polyketide intermediate. ClusterCAD can be accessed at https://clustercad.jbei.org and at http://clustercad.igb.uci.edu.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Energy Efficiency and Renewable Energy (EERE), Bioenergy Technologies Office (EE-3B); OpenEye Scientific Software, Santa Fe, NM (United States); ChemAxon, Budapest (Hungary); Defense Advanced Research Projects Agency (DARPA); National Science Foundation (NSF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1433111

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: D1 Vol. 46; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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