Hybrid peptide-polyketide natural products: Biosynthesis and prospects toward engineering novel molecules

Liangcheng Du, César Sánchez, Ben Shen

Research output: Contribution to journalReview article

144 Citations (Scopus)

Abstract

The structural and catalytic similarities between modular non-ribosomal 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.

Original languageEnglish (US)
Pages (from-to)78-95
Number of pages18
JournalMetabolic Engineering
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2001

Fingerprint

Peptide Synthases
Polyketide Synthases
Polyketides
Biosynthesis
Biological Products
Peptides
Molecules
Peptide Biosynthesis
Biosynthetic Pathways
Molecular Biology
Catalytic Domain

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Hybrid peptide-polyketide natural products : Biosynthesis and prospects toward engineering novel molecules. / Du, Liangcheng; Sánchez, César; Shen, Ben.

In: Metabolic Engineering, Vol. 3, No. 1, 01.01.2001, p. 78-95.

Research output: Contribution to journalReview article

@article{9e84b0b8488d4044aa20bf53ee2a40e7,
title = "Hybrid peptide-polyketide natural products: Biosynthesis and prospects toward engineering novel molecules",
abstract = "The structural and catalytic similarities between modular non-ribosomal 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.",
author = "Liangcheng Du and C{\'e}sar S{\'a}nchez and Ben Shen",
year = "2001",
month = "1",
day = "1",
doi = "10.1006/mben.2000.0171",
language = "English (US)",
volume = "3",
pages = "78--95",
journal = "Metabolic Engineering",
issn = "1096-7176",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Hybrid peptide-polyketide natural products

T2 - Biosynthesis and prospects toward engineering novel molecules

AU - Du, Liangcheng

AU - Sánchez, César

AU - Shen, Ben

PY - 2001/1/1

Y1 - 2001/1/1

N2 - The structural and catalytic similarities between modular non-ribosomal 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.

AB - The structural and catalytic similarities between modular non-ribosomal 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.

UR - http://www.scopus.com/inward/record.url?scp=0034796211&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034796211&partnerID=8YFLogxK

U2 - 10.1006/mben.2000.0171

DO - 10.1006/mben.2000.0171

M3 - Review article

C2 - 11162234

AN - SCOPUS:0034796211

VL - 3

SP - 78

EP - 95

JO - Metabolic Engineering

JF - Metabolic Engineering

SN - 1096-7176

IS - 1

ER -