Hybrid Peptide–Polyketide Natural Products: Biosynthesis and Prospects toward Engineering Novel Molecules
✍ Scribed by Liangcheng Du; César Sánchez; Ben Shen
- Publisher
- Elsevier Science
- Year
- 2001
- Tongue
- English
- Weight
- 450 KB
- Volume
- 3
- Category
- Article
- ISSN
- 1096-7176
No coin nor oath required. For personal study only.
✦ Synopsis
The structural and catalytic similarities between modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) inspired us to search for hybrid NRPS-PKS systems. By examining the biochemical and genetic data known to date for the biosynthesis of hybrid peptide-polyketide natural products, we show (1) that the same catalytic sites are conserved between the hybrid NRPS-PKS and normal NRPS or PKS systems, although the ketoacyl synthase domain in NRPS/PKS hybrids is unique, and (2) that specific interpolypeptide linkers exist at both the C- and N-termini of the NRPS and PKS proteins, which presumably play a critical role in facilitating the transfer of the growing peptide or polyketide intermediate between NRPS and PKS modules in hybrid NRPS-PKS systems. These findings provide new insights for intermodular communications in hybrid NRPS-PKS systems and should now be taken into consideration in engineering hybrid peptide-polyketide biosynthetic pathways for making novel "unnatural" natural products.