FIG 4.
Proposed pathway for CsA biosynthesis. (A) Bmt biosynthesis by the PKS pathway. The PKS SimG domains include the following: β-ketoacyl synthase (KS), acyltransferase (AT), dehydrogenase (DH), methyltransferase (MT), enoylreductase (ER), ketoreductase (KR), acyl carrier protein (ACP), S-adenosylmethionine (SAM). The chemical structure of compounds b1 to b3 and Bmt are shown. (B) Schematic structure of NRPS SimA and the machinery of CsA biosynthesis. There are 11 modules of SimA, and each module contains the condensation (C), adenylation (A), thiolation (T), and/or N-methylation (NM) domains. The terminal C domain (CT) is implicated in cyclization of the peptidyl chains to form CsA and its analogs. The cyclophilin SimC and exporter SimD may jointly contribute to cell tolerance of CSNs. Abu, aminobutyric acid; Sar, sarcocine; Nva, norvaline; MeLeu, methylleucine; aa, amino acids.