Post-translational modification of heterologously expressed Streptomyces type II polyketide synthase acyl carrier proteins

FEBS Lett. 1997 Apr 1;405(3):267-72. doi: 10.1016/s0014-5793(97)00202-0.

Abstract

Expression in Escherichia coli of Streptomyces acyl carrier proteins (ACPs) associated with polyketide biosynthesis using the pT7-7 expression system of Tabor and Richardson led to the production predominantly of inactive apo-proteins lacking the 4'-phosphopantetheinyl prosthetic group essential for polyketide synthase activity. Modification of growth conditions led to an increase of production of active holo-protein for the actinorhodin (act) ACP, but this technique was ineffective for oxytetracycline (otc) and griseusin (gris) ACPs. Labelling experiments revealed that a low level of otc ACP expressed prior to induction was produced mainly as active holo-protein, while post-induction 15N-labelled protein was almost exclusively in the apo-ACP form. Limiting endogenous holo-acyl carrier protein synthase (ACPS) concentration was implicated as responsible for low apo-ACP to holo-ACP conversion, rather than limiting substrate (coenzyme A) and cofactor (Mg2+) concentrations. Co-expression of act and gris ACPs with ACPS in E. coli led to high levels of production of active holo-ACPs and ACPS. We have also made the significant observation that ACPS is able to transfer acylated CoA moieties to act apo-ACP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Carrier Protein / metabolism*
  • Apoproteins / metabolism
  • Coenzyme A / metabolism
  • Disulfides
  • Escherichia coli / enzymology
  • Multienzyme Complexes / metabolism*
  • Protein Processing, Post-Translational
  • Recombinant Proteins
  • Species Specificity
  • Streptomyces / enzymology

Substances

  • Acyl Carrier Protein
  • Apoproteins
  • Disulfides
  • Multienzyme Complexes
  • Recombinant Proteins
  • Coenzyme A