Polyunsaturated fatty acid biosynthesis in myxobacteria: different PUFA synthases and their product diversity

Abstract

Polyunsaturated fatty acids (PUFAs), particularly the omega-3 long-chain PUFAs (LC-PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are well known for their beneficial health effects. The obvious limitation of the present EPA/DHA key source, fish oil, demands for alternative and sustainable PUFA resources and several biotechnological approaches addressing this problem are currently under development. Different marine microorganisms are known to produce PUFAs de novo under strictly anaerobic conditions employing polyketide synthase (PKS)-like enzymes known as PUFA synthases. Here, we report for the first time the characterization of such PUFA synthases from terrestrial origin. Two distinct types of PUFA biosynthetic gene clusters were discovered, originating from linoleic acid producing myxobacteria of the genus Sorangium as well as from species of the recently discovered myxobacterial genus Aetherobacter, that turned out to be prolific producers of EPA and DHA. The identified biosynthetic pathways differ significantly from the marine systems in terms of gene organization, catalytic domain arrangement, and sequence identity of the encoded PUFA synthases. Notably, a unique domain, which most likely acts as 1-acylglycerol-3-phosphate O-acyltransferase, was identified in these myxobacterial PUFA synthases. As the native producer strains grow slowly, are difficult to handle, and genetic modification has proven difficult, synthetic biotechnology approaches were applied to establish a heterologous production platform in the myxobacterial model strain Myxococcus xanthus.