A comprehensive overview on genomically directed assembly of aromatic polyketides and macrolide lactones using fungal megasynthases

Takayoshi Saruwatari, Alex P. Praseuth, Michio Sato, Kohei Torikai, Hiroshi Noguchi, Kenji Watanabe

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

Fungal polyketide synthases (PKSs) catalyze a carbon-carbon bond forming reaction in an iterative manner using a variety of acyl-CoA molecules as substrates when biosynthesizing complex polyketides. Although most members from this class of natural products exhibit notable biological activities, often they are naturally produced in trace levels or cultivation of the analyte-producing organism is less than feasible. Appropriately, to contend with the former challenge, one must identify any translational bottleneck and perform functional analysis of the associated enzymes. In recent years, many gene clusters purportedly responsible for biosynthesizing polyketides have been identified and cataloged from a variety of fungal genomes including genes coding for iterative PKSs, particulary bikaverin, zearalenone and hypothemycin biosynthetic enzymes. Mounting appreciation of these highly specific codons and their translational consequence will afford scientists the ability to anticipate the fungal metabolite by correlating an organism's genomic cluster to an appropriate biosynthetic system. It was observed in recent reports, the successful production of these recombinant enzymes using an Escherichia coli expression system which in turn conferred the anticipated metabolite in vitro. This review will focus on iterative PKSs responsible for biosynthesizing bikaverin, zearalenone and hypothemycin, and expand on befitting enzymatic reaction mechanisms and development of a highly versatile system that could potentially generate biologically active compounds.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalJournal of Antibiotics
Volume64
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

Fingerprint

Polyketide Synthases
Polyketides
Macrolides
Lactones
Zearalenone
Enzymes
Carbon
Fungal Genome
Acyl Coenzyme A
Multigene Family
Biological Products
Codon
Escherichia coli
Genes
bikaverin
hypothemycin

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

A comprehensive overview on genomically directed assembly of aromatic polyketides and macrolide lactones using fungal megasynthases. / Saruwatari, Takayoshi; Praseuth, Alex P.; Sato, Michio; Torikai, Kohei; Noguchi, Hiroshi; Watanabe, Kenji.

In: Journal of Antibiotics, Vol. 64, No. 1, 01.01.2011, p. 9-17.

Research output: Contribution to journalReview article

Saruwatari, Takayoshi ; Praseuth, Alex P. ; Sato, Michio ; Torikai, Kohei ; Noguchi, Hiroshi ; Watanabe, Kenji. / A comprehensive overview on genomically directed assembly of aromatic polyketides and macrolide lactones using fungal megasynthases. In: Journal of Antibiotics. 2011 ; Vol. 64, No. 1. pp. 9-17.
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