Molecular mechanisms in fungal fatty acid synthase (FAS) assembly

Fischer, M.; Mulinacci, B.; Joppe, M.; Vollrath, R.; Konstantinidis, K.; Koetter, P.; Ciccarelli, L.; Vonck, J.; Oesterhelt, D.; Grininger, M.

doi:10.1101/336578

bioRxiv · 10.1101/336578

Molecular mechanisms in fungal fatty acid synthase (FAS) assembly

Fischer, M.·Mulinacci, B.·Joppe, M.·Vollrath, R.·Konstantinidis, K.·Koetter, P.·Ciccarelli, L.·Vonck, J.·Oesterhelt, D.·Grininger, M.

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Abstract

The fungal fatty acid synthase (fFAS) multienzyme is a barrel-shaped 2.6 MDa complex comprising six times eight catalytic domains. Upon barrel-formation, up to several hundred kDa large polypeptides intertwine to bury about 170,000 [A]2 of protein surface. Functional, regulatory and structural data as well as evolutionary aspects of fFAS have been elucidated during the last decades. Notwithstanding a profound knowledge of this protein family, the biogenesis of the elaborate structure remained elusive. Remarkably, experimental data have recently demonstrated that fFAS self-assembles without the assistance of specific factors. Considering the infinitesimal probability that the barrel-shaped complex forms simply by domains approaching in the correct orientation, we were interested in understanding the sequence of events that have to orchestrate fFAS assembly. Here, we show that fFAS attains its quaternary structure along a pathway of successive domain-domain interactions, which is strongly related to the evolutionary development of this protein family. The knowledge on fFAS assembly may pave the way towards antifungal therapy, and further develops fFAS as biofactory in technological applications.

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Fischer, M., Mulinacci, B., Joppe, M., Vollrath, R., Konstantinidis, K., Koetter, P., Ciccarelli, L., Vonck, J., Oesterhelt, D., Grininger, M.. 2018-06-01. Molecular mechanisms in fungal fatty acid synthase (FAS) assembly. https://doi.org/10.1101/336578

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