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Cladosporin can be isolated from the fungus <jats:italic>Cladosporium cladosporioides<\/jats:italic>, where it is biosynthesized by a highly reducing (HR) and a non\u2010reducing (NR) iterative type\u2005I polyketide synthase (PKS) pair. Genome sequencing of the host organism and subsequent heterologous expression of these enzymes in <jats:italic>Saccharomyces cerevisiae<\/jats:italic> produced cladosporin, confirming the identity of the putative gene cluster. Incorporation of a pentaketide intermediate analogue indicated a 5+3 assembly by the HR PKS Cla2 and the NR PKS Cla3 during cladosporin biosynthesis. Advanced\u2010intermediate analogues were synthesized and incorporated by Cla3 to furnish new cladosporin analogues. A putative lysyl\u2010tRNA synthetase resistance gene was identified in the cladosporin gene cluster. Analysis of the active site emphasizes key structural features thought to be important in resistance to cladosporin.<\/jats:p>","DOI":"10.1002\/anie.201509345","type":"journal-article","created":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T12:31:54Z","timestamp":1448368314000},"page":"664-668","source":"Crossref","is-referenced-by-count":47,"title":["Production of New Cladosporin Analogues by Reconstitution of the Polyketide Synthases Responsible for the Biosynthesis of this Antimalarial Agent"],"prefix":"10.1002","volume":"55","author":[{"given":"Rachel V. 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