Fig. 2. Proposed mechanism for assembly of icosalide A1 (1) by IcoA. Domain and module organisation of the NRPS, showing the PCP-bound thioester intermediates proposed to be formed by each module. The CI domains initiate lipopeptide chain assembly by N-acylating the aminoacyl thioesters attached to the downstream PCP domains with 3-hydroxyacyl thioester intermediates in fatty acid biosynthesis. Abbreviations are as follows: A, adenylation domain; CI, chain initiating condensation domain; CE, bifunctional epimerisation–condensation domain; LCL, condensation domain that catalyses condensation of l-configured aminoacyl donor and acceptor substrates; PCP, peptidyl carrier protein domain; TE, thioesterase domain. The residues used to predict the substrate specificity of A-domains are shown in Table S3†.
