Title: Angucycline biosynthesis: from gene detection to enzymatic synthesis of novel metabolites

Presenter: Mikko Metsä-Ketelä, Ph.D.

University: Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland

Time:9:00-11:00, 7 April, 2011

Venue: A102, Institute of Microbiology, Chinese Academy of Sciences

Abstract: In this presentation Dr. Metsä-Ketelä will outline the studies towards understanding the biosynthesis of a group of aromatic polyketides, the angucyclines, which have been conducted in their laboratory over the past decade. A screening method was used to detect aromatic polyketide gene clusters in Streptomyces and related Actinobacteria, and revealed that approximately 45% of the 250 bacterial strains screened harboured an angucycline-type gene cluster, which was in sharp contrast to the number of angucycline metabolites reported in the literature. Subsequently, this lead to the isolation and characterization of the cryptic cab and pga gene clusters from Streptomyces sp. H021 and PGA64, respectively. Molecular genetic studies conducted confirmed that the biosynthetic genes isolated were, in effect, functional and that they could be used in combinatorial biosynthesis for the production of novel angucycline metabolites, the gaudimycins.

In the second part, Dr. Metsä-Ketelä will describe in more detail in vitro attempts to elucidate the closely coupled redox modification reaction cascades, which occur during post-PKS steps in the biosynthesis of several angucyclines. The enzyme components involved belong to two well-characterized families, NADPH-dependent flavoprotein hydroxylases and short-chain alcohol dehydrogenases. Utilization of a combination of spectrophotometric and fluorometric analyses has recently uncovered new insight into the individual reactions that occur within the “biosynthetic black box”. Finally, Dr. Metsä-Ketelä will briefly outline some future prospects and would like to introduce the term “combinatorial enzymatic synthesis”.