Harnessing the Natural Pool of Polyketide and Non-ribosomal Peptide Family: A Route Map towards Novel Drug Development

Abstract

: Emergence of communicable and non-communicable diseases possess health challenge to millions of people worldwide and is a major threat to the economic and social development in the coming century. The occurrence of recent pandemic, SARS-CoV-2 caused by lethal severe acute respiratory syndrome coronavirus 2 is one such example. Rapid research and development of drugs for the treatment and management of these diseases has been an incredibly challenging task for the pharmaceutical industry. Although, substantial focus has been made in the discovery of therapeutic compounds from natural sources having significant medicinal potential, their synthesis has shown a slow progress. Hence, the discovery of new targets by the application of the latest biotechnological and synthetic biology approaches is very much the need of the hour. Polyketides (PKs) and non-ribosomal peptides (NRPs) found in bacteria, fungi and plants are a large diverse family of natural products synthesized by two classes of enzymes: polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). These enzymes possess immense biomedical potential due to their simple architecture, catalytic capacity, as well as diversity. With the advent of latest in-silico and in-vitro strategies, these enzymes and their related metabolic pathways, if targeted, can contribute highly towards the biosynthesis of an array of potentially natural drug leads that have antagonist effects on biopolymers associated with various human diseases. In the face of the rising threat from the multidrug-resistant pathogens, this will further open new avenues for the discovery of novel and improved drugs by combining the natural and the synthetic approaches. This review discusses the relevance of polyketides and non-ribosomal peptides and the improvement strategies for the development of their derivatives and scaffolds, and how they will be beneficial to the future bioprospecting and drug discovery.

Analyzing the Influence of Clostridium butyricum on Liver Health in Spotted Sea Bass (Lateolabrax maculatus) via Transcriptomics and Metabolomics

“…In the metabolomics results, we also observed upregulation of polyketone unit biosynthesis, and polyketone metabolites have obvious antiviral effects (Girija et al 2022), suggesting that the antiviral capacity of the liver is improved with the participation of Clostridium butyrate. At the same time, we observed a signi cant upregulation of the renin-angiotensin system, which is a major player in blood pressure homeostasis (Sparks et al 2014), suggesting that the liver's ability to maintain blood pressure homeostasis is enhanced with CB.…”

Cell-free protein synthesis for nonribosomal peptide synthetic biology

“…Peptide natural products form the basis of many important molecules including agrochemicals (Cane et al, 1998;Pereira-Dias et al, 2023), bioproducts (Tao et al, 2023), and therapeutics (Corpuz et al, 2022;Girija et al, 2022). Of these applications, the most historically significant one has been as an important source for drug leads (Atanasov et al, 2015;Harvey et al, 2015).…”

Structural analysis unravels the functional promiscuity of Quinolone synthase-mediated polyketide biosynthesis in Aegle marmelos Correa

“…Polyketides (PKs) are chemically diverse natural products with immense pharmaceutical properties. PKs and their possible derivatives could be used as attractive starting points for the development of new bioactive molecules with clinical applications 1,2 . Polyketide synthases (PKS) are multifunctional enzymes that synthesize PKs in plants, fungi, and bacteria 3 .…”