Anthracimycin

In preliminary laboratory research, it has shown activity against Bacillus anthracis,[1] the bacteria that causes anthrax, and against methicillin-resistant Staphylococcus aureus (MRSA).

[2] Anthracimycin was first isolated from a species of marine Streptomyces (strain CNH365) which was collected off the shore of Santa Barbara, CA.

This modular synthetic pathway uses a trans-acyltransferase (AT) domain to load successive units of malonyl-CoA (MCoA) and methylmalonyl-CoA (MMCoA) to build the macrolide backbone.

[3] Anthracimycin was first noted for its potent activity against Bacillus anthracis (strain UM23C1-1), which is known to cause the human infectious disease anthrax, with a minimum inhibitory concentration (MIC) of 0.031 ug/mL.

[4][1] As part of an in vivo study with a murine peritonitis model of infection, anthracimycin was found to protect mice against mortality by MRSA at doses of 1 and 10 mg/kg.

Figure 1. Architecture of the anthracimycin type I PKS system. Outlined domains are used iteratively. ACP- acyl carrier protein, AD- alcohol dehydrogenase, AT- acyltransferase, D- docking domain, DH- dehydratase, KS- ketoacyl synthase, KR- ketoreductase, MT- methyltransferase, ER- enoylreductase, TE- thioesterase.
Figure 2. Formation of the decalin ring by [4+2] cycloaddition.