Bacterial natural products, particularly those found in streptomyces, play an important part in the production of bioactive metabolites. The angucycline group, denoted by the angled benz[α]anthracene polyketide-derived backbone, contains medically interesting chemical scaffolds comprised of diverse oligosaccharide chains differing in size, length, and linkage. Landomycin A, first extracted from <i>Streptomyces cyanogenus</i> (S-136), is one of the largest members of the angucycline family. This compound has been proven to have activity against a variety of cancer models. However, due to its toxicity, the compound has yet to be introduced to the clinic. This compound is understudied due to the lack of expeditious purification techniques. Outside of extraction from its host organism, fully synthetic methods towards landomycin A have been developed. However, these methods extremely long (63 total steps) and low yielding (&lt;0.02%). Seeing that total synthesis was not a viable route to efficient production of this metabolite, a bioengineered version of the original streptomyces strain was introduced to enhance landomycin A production by the organism. In this research, purification of the intended target out of this bacterial strain (S-136-9a) has been optimized to a scalable point. Herein, we establish the LD<sub>50</sub> and MIC values for the native landomycin A moiety. We intend to use synthetic methods to structurally derivatize the oligosaccharide chain. First, we plan to complete a systematic analysis of the structure-activity relationship (SAR) in cancer models, specifically multi-drug resistant versions. From those findings, we intend to make logical structural derivatizations to the parent molecule in the pursuit of a less toxic, more efficacious drug.

The improved purification and logical structural derivatization of Landomycin A, an angucycline antibiotic

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