Coalition of Biology and Chemistry for Ameliorating Antimicrobial Drug Discovery

Synthesis of Curcumin Glycosides with Enhanced Anticancer Properties Using One-Pot Multienzyme Glycosylation Technique

“…Hence, the targeted modification of already-identified bioactive compounds for enhancing their utility and potency is the most rational approach for fulfilling the commercial requirement of drugs. The rational integration of biological and chemical approaches is accelerating such drug development processes [59,60]. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is a nontoxic phytomolecule.…”

Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

“…Recent research indicated that the rate of new NP discovery has been maintained despite a drop in the number of compounds making it through regulatory approval pipelines [15]. However, the emergence of antibiotic-resistant pathogens or drug-resistant disease conditions and most of the NPs are not produced in significant titers or the biosynthetic gene clusters (BGCs) are cryptic, or the producer strains are not genetically tractable, which pose the greatest challenge for NPs based drug discovery [16][17][18]. In such cases production can be achieved in other production platforms as genetically tractable alternative hosts or suitable heterologous hosts [17][18][19].…”

“…The first approach can be tuning the production by altering physiological conditions, the use of elicitors/chemicals, and modulating the regulatory system in the native host. The second approach can be production in the rationally engineered heterologous host [18]. However, the heterologous expression suffers from various disadvantages, such as the limited efficiencies in the cloning of large BGCs; unavailability of a suitable expression platform; and incompatibility of the biosynthetic elements, such as biosynthetic precursors, regulations, and cofactors.…”

“…However, the heterologous expression suffers from various disadvantages, such as the limited efficiencies in the cloning of large BGCs; unavailability of a suitable expression platform; and incompatibility of the biosynthetic elements, such as biosynthetic precursors, regulations, and cofactors. These constraints provide strong support for the quest for mining NPs from native producers, including genetic and chemical induction-based approaches [18,24]. Moreover, it is evident that a single potent Streptomyces encodes more than 20-30 BGCs for diverse bioactive compounds among them most of them are cryptic, but it is not feasible to transfer all BGCs to heterologous host in the single setting.…”

“…Therefore, the tuning or activation of the cryptic BGCs by the chemical modulation or the genetic intersection in the native host provides a tremendous opportunity for obtaining targeted, as well as untargeted NPs. Thus, this approach in most cases uncovers the unprecedented discovery of novel chemical structures with efficient biological activities [18]. In addition, the engineering/modulation steps may be less rigorous than the optimizations required in heterologous expressions, which requires rigorous steps of host selection and cloning, and in most cases, engineering of the producer host, optimizing the media components, and even the perturbation of regulation systems [24].…”