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Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from <jats:italic>S. scabies<\/jats:italic>, along with genes encoding a promiscuous tryptophan synthase (TrpS) from <jats:italic>Salmonella typhimurium<\/jats:italic>, were assembled in a heterologous host <jats:italic>Streptomyces albus<\/jats:italic>. Upon feeding indole derivatives to the engineered <jats:italic>S. albus<\/jats:italic> strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to \u201cnon\u2010natural\u201d product target compounds.<\/jats:p>","DOI":"10.1002\/anie.201801525","type":"journal-article","created":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T02:07:03Z","timestamp":1522462023000},"page":"6830-6833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["De novo Biosynthesis of \u201cNon\u2010Natural\u201d Thaxtomin Phytotoxins"],"prefix":"10.1002","volume":"57","author":[{"given":"Michael","family":"Winn","sequence":"first","affiliation":[{"name":"School of Chemistry Manchester Institute of Biotechnology The University of Manchester  131 Princess Street Manchester M1 7DN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Francis","sequence":"additional","affiliation":[{"name":"School of Chemistry Manchester Institute of Biotechnology The University of Manchester  131 Princess Street Manchester M1 7DN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8951-4873","authenticated-orcid":false,"given":"Jason","family":"Micklefield","sequence":"additional","affiliation":[{"name":"School of Chemistry Manchester Institute of Biotechnology The University of Manchester  131 Princess Street Manchester M1 7DN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,8]]},"reference":[{"key":"e_1_2_2_1_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NP00099H"},{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NP00109A"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608589103"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01453-14"},{"key":"e_1_2_2_5_1","unstructured":"A. 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