GRINS: Genetic elements that recode assembly-line polyketide synthases and accelerate their diversification
Aleksandra Nivina, Sur Herrera Paredes, Hunter B. Fraser, Chaitan Khosla
Abstract
Significance Assembly-line polyketide synthases (PKSs) make many medicinally significant natural products. A better understanding of evolutionary mechanisms underlying polyketide diversification could open new avenues for PKS engineering and drug discovery. In the course of interrogating the role of gene conversion in assembly-line PKS evolution, we discovered not only that gene conversion is widespread in these PKSs but also that it is frequently associated with the presence of a genetic element, which we have designated GRINS (genetic repeats of intense nucleotide skew). Computational analysis suggests that the presence of GRINS may promote late-stage structural diversification of polyketide antibiotics. Our work sets the stage for further investigation of the underlying molecular mechanisms and evolutionary roles of these genetic elements.