*2.3. Biosynthesis of Candicidin*

Candicidin is a 38-membered ring polyene macrolide produced by *Streptomyces griseus* IMRU 3570 that has antifungal activity. Like the other polyene compounds, the antifungal mechanism of candicidin is also by disrupting the fungal cell membrane. Candicidin has both the amino sugar mycosamine and the aromatic component p-aminoacetophenone in its macrolide structure [43,50].

The candicidin biosynthetic gene cluster (<205 kb) was cloned and partially sequenced. Four genes, canP1, canP3, canP2 (incomplete), and canPF (incomplete), were determined as genes encoding parts of type I PKSs (CanP1, CanP2, CanP3, and CanPF). CanP1 contains one loading domain and one module; CanP2 consists of three modules; and CanP2 comprises six modules. CanPF hypothetically serves as one end of the PKS gene cluster. The starter unit is PABA (p-aminobenzoic acid), and the extender units are four methylmalonyl-CoAs and 17 malonyl-CoAs. At the end of the process in PKS, the molecule is released by thioesterase (CanT). In the next step, the compound is cyclized to become candicidin aglycone, oxidized by P450 monooxygenase (CanC) with aid from ferredoxin (CanF). The last step is glycosylation by adding mycosamine to the structure [43,44].

**Figure 4.** Biosynthesis of rapamycin. ACP, acyl carrier protein; AT, acyltransferase; KS, ketosynthase; KR, ketoreductase; DH, dehydratase; ER, enoylreductase; PIE, pipecolate-incorporating enzyme. Adapted with permission from Schwecke, T.; Aparicio, J.F.; Molnár, I.; König, A; Khaw, L.E.; Haydock, S.F.; Oliynyk, M.; Caffrey, P.; Cortés, J.; Lester, J.B. The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc. Natl. Acad. Sci. USA 1995, 92, 7839–7843, doi:10.1073/pnas.92.17.7839 [34]. Copyright (1995) National Academy of Sciences, U.S.A. Adapted with permission of The Royal Society of Chemistry 2001, from Staunton, J.; Weissman, K.J. Polyketide biosynthesis: A millennium review. *Nat. Prod. Rep.* **2001**, *18*, 380–416 [26]; permission conveyed through Copyright Clearance Center, Inc.
