Abstract
Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. These compounds may serve as potential drug leads. This review summarizes the insights gained from research on type III PKSs, from the discovery of chalcone synthase in plants to novel PKSs in bacteria and fungi. To date, at least 15 families of type III PKSs have been characterized, highlighting the utility of PKSs in the development of natural product libraries for therapeutic development.
Highlights
Substantial focus has been awarded to polyketide research since its initial discovery about a century ago [1]
This review summarizes the insights gained from research on type III polyketide synthases (PKSs), engineering and structural characterization of PKSs have facilitated the use of target enzymes as frombiocatalysts the discovery of chalcone synthase inoptimized plants topolyketides
By rationally incorporating amino acid substitutions, the active site cavity of type III PKSs can be altered or expanded to facilitate the synthesis of more complex polyketides. This characteristic makes type III PKSs great candidates for structure-based engineering approaches to expand the chemical and structural diversity of natural products derived from these systems
Summary
Substantial focus has been awarded to polyketide research since its initial discovery about a century ago [1]. Substantial focus has been awarded to polyketide research since its initial discovery about a century in bacteria, and are plants Manyand of these bioactive natural products haveproduced significant medical or ago [1]. Fungi, Polyketides structurally functionally diverse secondary metabolites in bacteria, agricultural applications [2],of such asbioactive rapamycin Many these natural products immunosuppressant) have significant medical[3], or lovastatin agricultural(used applications [2], such as rapamycin (a macrolide immunosuppressant). [5], and resveratrol (reported anti-ageing properties in model organisms) [6] (Figure 1) This highlights the vital role polyketides and organisms) [6]. This highlights the vital role polyketides their anti-ageing derivativesproperties can play in in model the development of
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