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J. Microbiol. Biotechnol. 2015; 25(10): 1648-1652

Published online October 28, 2015 https://doi.org/10.4014/jmb.1504.04086

Copyright © The Korean Society for Microbiology and Biotechnology.

A New Protein Factor in the Product Formation of Non-Reducing Fungal Polyketide Synthase with a C-Terminus Reductive Domain

Bijinu Balakrishnan 1, Ramya Chandran 1, Si-Hyung Park 2 and Hyung-Jin Kwon 1*

1Division of Bioscience and Bioinformatics, Myongji University, Yongin 449-728, Republic of Korea, 2Department of Oriental Medicine Resources and Institute for Traditional Korean Medicine Industry, Mokpo National University, Muan 534-729, Republic of Korea

Received: April 30, 2015; Accepted: June 12, 2015

Abstract

Azaphilone polyketides are synthesized by iterative non-reducing fungal polyketide
synthases (NR-fPKSs) with a C-terminus reductive domain (-R). Several azaphilone
biosynthetic gene clusters contain a putative serine hydrolase gene; the Monascus azaphilone
pigment (MAzP) gene cluster harbors mppD. The MAzP productivity was significantly
reduced by a knockout of mppD, and the MAzP NR-fPKS-R gene (MpPKS5) generated its
product in yeast only when co-expressed with mppD. Site-directed mutations of mppD for
conserved Ser/Asp/His residues abolished the product formation from the MpPKS5/mppD
co-expression. MppD and its homologs are thus proposed as a new protein factor involved in
the product formation of NR-fPKS-R.

Keywords: Monascus pigment, azaphilone polyketide, non-reducing fungal polyketide synthase, MppD, Ser/Asp/His catalytic triad