Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A

• Published in: ChemBioChem
• Main Authors: Erol, Özlem, Schäberle, Till F., Schmitz, Alexander, Rachid, Shwan, Gurgui, Cristian, El Omari, Mustafa, Lohr, Friederike, Kehraus, Stefan, Piel, Jörn, Müller, Rolf, König, Gabriele M.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2010
• Subjects: Carbonic acid
• Online Access: http://dx.doi.org/10.1002/cbic.201000085; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbic.201000085; https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201000085

Abstract Corallopyronin A is a myxobacterial compound with potent antibacterial activity. Feeding experiments with labelled precursors resulted in the deduction of all biosynthetic building blocks for corallopyronin A and revealed an unusual feature of this metabolite: its biosynthesis from two chains, one solely PKS‐derived and the other NRPS/PKS‐derived. The starter molecule is believed to be carbonic acid or its monomethyl ester. The putative corallopyronin A biosynthetic gene cluster is a trans‐AT‐type mixed PKS/NRPS gene cluster, containing a β‐branching cassette. Striking features of this gene cluster are a NRPS‐like adenylation domain that is part of a PKS‐type module and is believed to be responsible for glycine incorporation, as well as split modules with individual domains occurring on different genes. It is suggested that CorB is a trans‐acting ketosynthase and it is proposed that it catalyses the Claisen condensation responsible for the interconnection of the two chains. Additionally, the stereochemistry of corallopyronin A was deduced by a combination of a modified Mosher's method and ozonolysis with subsequent chiral GC analyses.