Production of Effective Phyto-antimicrobials via Metabolic Engineering Strategies

Abstract

The emerging outbreak of infectious diseases poses a challenge and threatens human survival. The indiscriminate use and drying pipelines of antibiotic arsenals have led to the alarming rise of drug-resistant pathogens, projecting a serious concern. The rising antimicrobial resistance and redundancy of antibiotic discovery platforms (ADPs) have highlighted the growing concern to discover new antibiotics, necessitating exploring natural products as effective alternatives to counter drug resistance. Recently, plants have been extensively investigated in search of the "phytotherapeutics", attributed to their potential efficacy and tackling the majority of the drug-resistant mechanisms, including biofilms, efflux pumps, cell communication, and membrane proteins. However, major challenges in geographical fluctuations, low plant concentration, and over-harvestation of natural resources restrict availability and complete utilization of phyto-therapeutics as antimicrobials. Recent advances in scientific interventions have been instrumental in producing novel antimicrobials via metabolic engineering approaches in plant systems. The progress in plant genome editing, pathway reconstitution, and expression has defined new paradigms in the successful production of antimicrobials in the post-antibiotic era. The thematic review discusses the existing and emerging significance of phytotherapeutics in tackling antimicrobial resistance and employing metabolic engineering approaches. The prevailing scenario of antimicrobial resistance and the mechanisms, the traditional and modern drug-discovery approaches in addressing antimicrobial resistance, emphasizing advances in metabolic engineering approaches for antimicrobial production, and the plausible solutions for tackling drug-resistant pathogens, forms the key theme of the article.

Keywords: Antibiotic discovery platforms; Antimicrobial resistance; Drug-resistant pathogens; Metabolic engineering; Natural products; One-Health concept; Phyto-therapeutics.