cr9b00525_si_001.pdf (303.61 kB)
Evolution and Diversity of Assembly-Line Polyketide Synthases
journal contribution
posted on 2019-12-15, 13:03 authored by Aleksandra Nivina, Kai P. Yuet, Jake Hsu, Chaitan KhoslaAssembly-line polyketide synthases (PKSs) are among the
most complex
protein machineries known in nature, responsible for the biosynthesis
of numerous compounds used in the clinic. Their present-day diversity
is the result of an evolutionary path that has involved the emergence
of a multimodular architecture and further diversification of assembly-line
PKSs. In this review, we provide an overview of previous studies that
investigated PKS evolution and propose a model that challenges the
currently prevailing view that gene duplication has played a major
role in the emergence of multimodularity. We also analyze the ensemble
of orphan PKS clusters sequenced so far to evaluate how large the
entire diversity of assembly-line PKS clusters and their chemical
products could be. Finally, we examine the existing techniques to
access the natural PKS diversity in natural and heterologous hosts
and describe approaches to further expand this diversity through engineering.