Abstract
Fungal hybrid polyketide synthase-nonribosomal peptide synthetases (PKS-NRPSs) significantly expand the diversity and functionalities of polyketide metabolites by fusing diverse polyketide backbones with a range of amino acids of different chemical properties. This gives rise to a plethora of polyketide acyl-aminoacyl chains that are further diversified by the mechanism of release and post-PKS-NRPS processing. Using selected examples from biosynthetic studies, this article provides an overview of the fungal PKS-NRPS biosynthetic logic, with emphasis on the strategies that introduce structural diversity and complexity to PKS-NRPS products. We have divided the common strategies into: (1) variations in polyketide branching and functional group modifications, (2) selection and incorporation of amino acids, (3) release mechanisms, and (4) post-PKS-NRPS cyclization/rearrangement of the polyketide-amino acid backbone. The prospects and challenges of engineering fungal PKS-NRPS hybrids are also discussed.
| Original language | English |
|---|---|
| Title of host publication | Comprehensive Natural Products III |
| Subtitle of host publication | Chemistry and Biology |
| Editors | Hung-Wen (Ben) Liu, Tadhg P. Begley |
| Publisher | Elsevier |
| Pages | 415-444 |
| Volume | 1 |
| Edition | 3 |
| ISBN (Print) | 978-0-08-102691-5 |
| DOIs | |
| Publication status | Published - 2020 |