Enhanced undecylprodigiosin production using collagen hydrolysate: a cost-effective and high-efficiency synthesis strategy

Undecylprodigiosin (UDP), a desirable pyrrole-based biomaterial, holds significant promise in pharmaceutical and medical applications due to its diverse biological activities. However, its application is usually hampered by low synthesis efficiency and high production costs. Here, we developed a high-efficiency and cost-effective strategy for UDP synthesis using collagen hydrolysate (COH) as a readily available and abundant precursor source in conjunction with <i>Streptomyces</i> sp. SLL-523. COH obviously accelerated the proliferation of <i>Streptomyces</i> sp. SLL-523. Replacing muscle hydrolysate with COH resulted in a 7-fold increase in UDP yield and a 10-fold reduction in fermentation time, indicating that COH significantly enhanced the synthesis efficiency of UDP. Besides, COH remarkably increased the intracellular levels of UDP precursor amino acids (AAs). Whole-genome analysis of <i>Streptomyces</i> sp. SLL-523 revealed the gene clusters responsible for UDP synthesis and COH utilization. COH markedly stimulated the expression of genes involved in the metabolism pathways of energy, transporters, peptides, and AAs, ultimately promoting the UDP synthesis. Significantly, COH efficiently triggered and boosted the expression of key genes in the UDP biosynthesis pathway, including <i>redQ</i>, <i>redM</i>, <i>redN</i>, and <i>redL</i>, leading to highly efficient UDP synthesis. Thus, this innovative approach provides a novel framework for the high-efficiency synthesis of natural pyrrole biomedical materials based on renewable nitrogen-contained biomass.