{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T22:39:52Z","timestamp":1775860792137,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"publisher","award":["EE0008926"],"award-info":[{"award-number":["EE0008926"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DOE Joint BioEnergy Institute","award":["DEAC02-05CH11231"],"award-info":[{"award-number":["DEAC02-05CH11231"]}]},{"DOI":"10.13039\/100019193","name":"Philomathia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019193","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Megasynthase enzymes such as type I modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) play a central role in microbial chemical warfare because they can evolve rapidly by shuffling parts (catalytic domains) to produce novel chemicals. If we can understand the design rules to reshuffle these parts, PKSs and NRPSs will provide a systematic and modular way to synthesize millions of molecules including pharmaceuticals, biomaterials, and biofuels. However, PKS and NRPS engineering remains difficult due to a limited understanding of the determinants of PKS and NRPS fold and function. We developed ClusterCAD to streamline and simplify the process of designing and testing engineered PKS variants. Here, we present the highly improved ClusterCAD 2.0 release, available at https:\/\/clustercad.jbei.org. ClusterCAD 2.0 boasts support for PKS-NRPS hybrid and NRPS clusters in addition to PKS clusters; a vastly enlarged database of curated PKS, PKS-NRPS hybrid,\u00a0and NRPS clusters; a diverse set of chemical \u2018starters\u2019 and loading modules; the new Domain Architecture Cluster Search Tool; and an offline Jupyter Notebook workspace, among other improvements. Together these features massively expand the chemical space that can be accessed by enzymes engineered with ClusterCAD.<\/jats:p>","DOI":"10.1093\/nar\/gkac1075","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T11:12:36Z","timestamp":1669201956000},"page":"D532-D538","source":"Crossref","is-referenced-by-count":25,"title":["ClusterCAD 2.0: an updated computational platform for chimeric type I polyketide synthase and nonribosomal peptide synthetase design"],"prefix":"10.1093","volume":"51","author":[{"given":"Xavier B","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of California , Berkeley , CA \u00a094720, USA"},{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory , Berkeley , CA \u00a094720, USA"}]},{"given":"Sarah","family":"LaFrance","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory , Berkeley , CA \u00a094720, USA"},{"name":"Biofuels and Bioproducts Division, Joint BioEnergy Institute , 5885 Hollis Street , Emeryville , CA \u00a094608, USA"},{"name":"QB3 Institute, University of California , Berkeley , CA \u00a094720, USA"}]},{"given":"Yifei","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Sciences, University of California , Berkeley , CA \u00a094720, USA"}]},{"given":"Alberto A","family":"Nava","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory , Berkeley , CA \u00a094720, USA"},{"name":"Department of Chemical and Biomolecular Engineering, University of California , Berkeley , CA \u00a094720, USA"}]},{"given":"Hector\u00a0Garcia","family":"Martin","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory , Berkeley , CA \u00a094720, USA"},{"name":"Biofuels and Bioproducts Division, Joint BioEnergy Institute , 5885 Hollis Street , Emeryville , CA \u00a094608, USA"},{"name":"Department of Energy Agile BioFoundry , Emeryville , CA \u00a094608, USA"}]},{"given":"Jay\u00a0D","family":"Keasling","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory , Berkeley , CA \u00a094720, USA"},{"name":"Biofuels and Bioproducts Division, Joint BioEnergy Institute , 5885 Hollis Street , Emeryville , CA \u00a094608, USA"},{"name":"Department of Chemical and Biomolecular Engineering, University of California , Berkeley , CA \u00a094720, USA"},{"name":"Department of Bioengineering, University of California , Berkeley , CA \u00a094720, USA"},{"name":"QB3 Institute, University of California , Berkeley , CA \u00a094720, USA"},{"name":"Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark \u00a0 2800 Copenhagen , Denmark"},{"name":"Center for Synthetic Biochemistry, Institute for Synthetic Biology, Shenzhen Institutes for Advanced Technologies , Shenzhen , China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6056-353X","authenticated-orcid":false,"given":"Tyler\u00a0W H","family":"Backman","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory , Berkeley , CA \u00a094720, USA"},{"name":"Biofuels and Bioproducts Division, Joint BioEnergy Institute , 5885 Hollis Street , Emeryville , CA \u00a094608, USA"}]}],"member":"286","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"2023010804181564000_B1","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/nrmicro1287","article-title":"Combinatorial biosynthesis of reduced polyketides","volume":"3","author":"Weissman","year":"2005","journal-title":"Nat. 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