Enhancing Geranylgeranyl Pyrophosphate Supply in Engineered Cyanobacteria for Improved Production of Natural Pigments and Terpenoid Precursors

Abstract

Geranylgeranyl pyrophosphate (GGPP) is a key precursor for carotenoids, chlorophyll derivatives, and numerous high-value isoprenoids used in food, nutraceutical, and pharmaceutical industries. Microbial and photosynthetic production approaches offer promising alternatives to conventional plant extraction and chemical synthesis; however, further optimization and comprehensive sustainability assessments are required for industrial implementation. In this study, a photosynthetic production platform was developed by redirecting carbon flux in Synechocystis sp. PCC 6803 to enhance GGPP production via activation of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Two engineered mutants, ΔP (deficient in poly(3-hydroxybutyrate) synthesis) and ΔGP (deficient in both glycogen and poly(3-hydroxybutyrate) synthesis), were evaluated alongside the wild-type (WT) strain under multiple physiological conditions, including carbon supplementation and UV radiation. Redirecting cellular carbon metabolism significantly enhanced pigment accumulation and overall isoprenoid biosynthesis, with ΔGP strain showing the greatest improvement. Elevated intracellular GGPP levels were observed under all tested conditions, with the highest concentrations obtained under glucose supplementation and UV treatment. The best-performing strain exhibited approximately twelvefold increase in GGPP content relative to the control. These findings demonstrate that rational metabolic engineering of cyanobacteria can markedly improve precursor supply for isoprenoid synthesis, establishing an efficient photosynthetic platform for producing natural pigments, flavor compounds, and other value-added bioproducts.