Biosynthesis of aromatic polyketides in microorganisms using type II polyketide synthases

Jia Wang,Yajun Yan,Ruihua Zhang,Qipeng Yuan,Xinxiao Sun,Xiaolin Shen,Xin Chen

doi:10.1186/s12934-020-01367-4

Abstract

Aromatic polyketides have attractive biological activities and pharmacological properties. Different from other polyketides, aromatic polyketides are characterized by their polycyclic aromatic structure. The biosynthesis of aromatic polyketides is usually accomplished by the type II polyketide synthases (PKSs), which produce highly diverse polyketide chains by sequential condensation of the starter units with extender units, followed by reduction, cyclization, aromatization and tailoring reactions. Recently, significant progress has been made in characterization and engineering of type II PKSs to produce novel products and improve product titers. In this review, we briefly summarize the architectural organizations and genetic contributions of PKS genes to provide insight into the biosynthetic process. We then review the most recent progress in engineered biosynthesis of aromatic polyketides, with emphasis on generating novel molecular structures. We also discuss the current challenges and future perspectives in the rational engineering of type II PKSs for large scale production of aromatic polyketides.

Highlights

Polyketides are structurally diverse and biologically active secondary metabolites derived from natural sources such as animals, plants, fungi and bacteria [1]
The type I polyketide synthases (PKSs) can be further classified into iterative type I PKSs (Fig. 1a) and modular type I PKSs (Fig. 1b) [12]. iPKSs are mainly found in fungi and the domains are used repeatedly to catalyze multiple rounds of elongation [13, 14]
Natural products derived from plants, animals and microorganisms are widely used in food, cosmetic, chemical and pharmaceutical industries

Summary

Introduction

Polyketides are structurally diverse and biologically active secondary metabolites derived from natural sources such as animals, plants, fungi and bacteria [1]. Type II PKSs are mainly responsible for producing aromatic polyketides by catalyzing iterative Claisen condensation reaction usually using acetate as the starter unit [19]. Otten et al identified a gene cluster dnr encoding type II PKS which can employ propionyl-CoA as the starter unit for the production of daunorubicin and doxorubicin, two famous anthracycline topoisomerase inhibitors, in Streptomyces spp.

Results

Conclusion