Medium-chain fatty acids affect citrinin production in the filamentous fungus Monascus ruber

During submerged culture in the presence of glucose and glutamate, the fila mentous fungus Monascus ruber produces water-soluble red pigments together with citrinin, a mycotoxin with nephrotoxic and hepatoxic effects on animal s. Analysis of the C-13-pigment molecules from mycelia cultivated with [1-C -13]-, [2-C-13]-, or [1,2-C-13]acetate by C-13 nuclear magnetic resonance i ndicated that the biosynthesis of the red pigments used both the polyketide pathway, to generate the chromophore structure, and the fatty acid synthes is pathway, to produce a medium-chain fatty acid (octanoic acid) which was then bound to the chromophore by a transesterification reaction. Hence, to enhance pigment production, we tried to short-circuit the de novo synthesis of medium-chain fatty acids by adding them to the culture broth. Of fatty acids with carbon chains ranging from 6 to 18 carbon atoms, only octanoic a cid showed a 30 to 50% stimulation of red pigment production, by a mechanis m which, in contrast to expectation, did not involve its direct trans-ester ification on the chromophore backbone. However, the medium- and long-chain fatty acids tested were readily assimilated by the fungus, and in the case of fatty acids ranging from 8 to 12 carbon atoms, 30 to 40% of their initia l amount transiently accumulated in the growth medium in the form of the co rresponding methylketone 1 carbon unit shorter. Very interestingly, these f atty acids or their corresponding methylketones caused a strong reduction i n, or even a complete inhibition of, citrinin production by M, ruber when t hey were added to the medium. Several data indicated that this effect could be due to the degradation of the newly synthesized citrinin (or an interme diate in the citrinin pathway) by hydrogen peroxide resulting from peroxiso me proliferation induced by medium-chain fatty acids or methylketones.