Work

TDP- l -Megosamine Biosynthesis Pathway Elucidation and Megalomicin A Production in Escherichia coli

Year: 2010

Type: article

Abstract: In vivo reconstitution of the TDP-l-megosamine pathway from the megalomicin gene cluster of Micromonospora megalomicea was accomplished by the heterologous expression of its biosynthetic genes in Escherichia coli. Mass spectrometric analysis of the TDP-sugar intermediates produced from operons containing different sets of genes showed that the production of TDP-l-megosamine from TDP-4-keto-6-deoxy-d-glucose requires only five biosynthetic steps, catalyzed by MegBVI, MegDII, MegDIII, MegDIV, and MegDV. Bioconversion studies demonstrated that the sugar transferase MegDI, along with the helper protein MegDVI, catalyzes the transfer of l-megosamine to either erythromycin C or erythromycin D, suggesting two possible routes for the production of megalomicin A. Analysis in vivo of the hydroxylation step by MegK indicated that erythromycin C is the intermediate of megalomicin A biosynthesis.

Source: Applied and Environmental Microbiology

DOI: 10.1128/aem.03083-09

Authors: Mariana Useglio, Salvador Peirú, Eduardo Rodríguez, Guillermo R. Labadie, John R. Carney, Hugo Gramajo

Institutions: Consejo Nacional de Investigaciones Científicas y Técnicas, National University of Rosario, Instituto de Biología Molecular y Celular de Rosario, Kosan Biosciences (United States)

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: Consejo Nacional de Investigaciones Científicas y Técnicas, Agencia Nacional de Promoción Científica y Tecnológica

OpenAlex ID: W2012144319

FWCI: 0.704

Cites: 32

Cited by: 20

Related to: 10