Journal
JOURNAL OF NATURAL PRODUCTS
Volume 69, Issue 3, Pages 387-393Publisher
AMER CHEMICAL SOC
DOI: 10.1021/np050467t
Keywords
-
Funding
- NCI NIH HHS [U19 CA113297-01, U19 CA113297, CA113297, R01 CA106150, CA106150, R01 CA106150-03] Funding Source: Medline
- NIAID NIH HHS [AI51689, K02 AI051689, K02 AI051689-05] Funding Source: Medline
Ask authors/readers for more resources
A fundamental feature of modular polyketide synthases (PKSs) is the highly predictable relationship between the domain order and the chemical functional groups of resultant polyketide products. Sequence analysis and biochemical characterization of the leinamycin (LNM) biosynthetic gene cluster from Streptomyces atroolivaceus S-140 has revealed a gene, lnmJ, that encodes five PKS modules but with six acyl carrier protein (ACP) domains. The LnmJ PKS module 6 contains two ACP domains, ACP(6-1) and ACP(6-2), separated by a C-methyltransferase domain. Site-directed mutagenesis experiments were carried out with each of these ACPs to test alternative mechanisms proposed for their role in polyketide chain elongation. The in vivo results revealed a new type of polyketide chain skipping mechanism, in which either ACP is sufficient for LNM biosynthesis. Biochemical characterization in vitro showed that both ACPs can be loaded with a malonate extender unit by the LnmG acyl transferase; however, ACP(6-2) appears to be preferred because the loading efficiency is about 5-fold that of ACP(6-1). The results are consistent with ACP(6-2) being used for the initial chain elongation step wth ACP(6-1) being involved in the ensuing C-methylation process. These findings provide new insights into the polyketide chain skipping mechanism for modular PKSs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available