Highly Efficient Production of Tailored Monascus Pigments by Using a Biocompatible Chemical Reaction Interfacing with Microbial Metabolism

Abstract

A biocompatible reaction interfacing with microbial metabolism is an efficient approach for production of desired chemicals. Monascus pigments are a traditional natural food colorant from a microbial source. The major color components are red Monascus pigments (RMPs) with various primary amine resides as well as some minor components of yellow ones (YMPs) and orange ones (OMPs). Herein, we elucidate the pathway of OMP degradation involving nucleophilic attack of water on OMPs for the first time. On the basis of OMP degradation and the conversion of OMPs into RMPs sharing a similar reaction mechanism, i.e., nucleophilic attack of water or primary amine on the activated OMPs, we design cascade reactions including biosynthesis of OMPs and biocompatible chemical conversion of OMPs into the stable RMPs with a single glycine residue using a flexible combining chemocatalyst (phosphate ion) and micellar catalyst (Triton X-100). The cascade reactions ensure that OMPs maintain a very low concentration during microbial fermentation by rapid chemical conversion of OMPs into the stable RMPs. In this way, the metabolite profile of microbial fermentation is tailored to RMPs with a single glycine residue as the major color components while free of OMPs and YMPs. Meanwhile, the possible OMP degradation as well as feedback inhibition is eliminated, and a high concentration of RMPs 3.2 mM (1.4 g/L) is also achieved. Designing cascade reactions also has potential for the efficient microbial fermentation of other azaphilone alkaloids.