![]() Molecules manufactured by type II PKSs include important antibiotics such as tetracycline and doxorubicin and anticancer agents such as doxycycline. coliīecause of the chemical diversity of this class of molecules and their strong track record for serving as widely used therapeutic agents. The products of type II PKSs are particularly lucrative targets for heterologous expression in E. Is an effective strategy for the study of polyketide synthases (PKSs), multienzyme assembly lines encoded by BGCs that manufacture an array of pharmaceutically relevant chemicals. Have emerged as popular heterologous host species for such applications due to their straightforward culture conditions, rapid growth, well-studied genetics, and flexibility for protein expression. Several genetically engineered strains of Escherichia coli Therefore, identifying a heterologous expression system to produce the enzymes encoded within BGCs is an important step toward harnessing biosynthetic proteinĪssembly lines for access to new chemical diversity. Products from disparate sources into one strain, thereby saving both time and resources. ![]() ![]() This approach can also centralize the production of target protein Heterologous expression of the proteins encoded by BGCs can bypass these issues, opening the door for the investigation of previously out-of-reach products. However, the chemical innovation coordinated by the enzymes encoded in these BGCs is often difficult to access, as the native organisms harboring BGCs of interest are often resistant to culture under laboratory conditions. Because biosynthesis mediated by these enzyme assemblies requires only earth-abundant, natural starting materials and uses water as a solvent, mixing-and-matching enzymes encoded by different BGCs could provide cost-effective and sustainable access to a host of pharmaceutically relevant “unnatural natural products.” Further biochemical and structural analyses of enzymes encoded by BGCs are necessary to make these goals a reality. These molecules, known as specialized metabolites (and commonly referred to as secondary metabolites or, more broadly, natural products), play a central role in medicine both as therapeutics and as inspiration for new pharmaceutically relevant compounds. BGCs encode suites of enzymes that cooperate to manufacture molecules thought to mediate an organism’s ecological interactions. Of intriguing biosynthetic gene clusters (BGCs) in a large swath of organisms. Recent technical advances in bioinformatics and computational biology have led to the discovery
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