Phycobiliproteins (PBPs) are colored and water-soluble biliproteins found in cyanobacteria, rhodophytes, cryptomonads and cyanelles. They are divided into three main types: allophycocyanin, phycocyanin and phycoerythrin, according to their spectral properties. There are two methods for PBPs preparation. One is the extraction and purification of native PBPs from Cyanobacteria, Cryptophyta and Rhodophyta, and the other way is the production of recombinant PBPs by heterologous hosts. Apart from their function as light-harvesting antenna in photosynthesis, PBPs can be used as food colorants, nutraceuticals and fluorescent probes in immunofluorescence analysis. An increasing number of reports have revealed their pharmaceutical potentials such as antioxidant, anti-tumor, anti-inflammatory and antidiabetic effects. The advances in PBP biogenesis make it feasible to construct novel PBPs with various activities and produce recombinant PBPs by heterologous hosts at low cost. In this review, we present a critical overview on the productions, characterization and pharmaceutical potentials of PBPs, and discuss the key issues and future perspectives on the exploration of these valuable proteins.

Succinic acid, a dicarboxylic acid produced as an intermediate of the tricarboxylic acid (TCA) cycle, is one of the most important platform chemicals for the production of various high value-added derivatives. As traditional chemical synthesis processes suffer from nonrenewable resources and environment pollution, succinic acid biosynthesis has drawn increasing attention as a viable, more environmentally friendly alternative. To date, several metabolic engineering approaches have been utilized for constructing and optimizing succinic acid cell factories. In this review, different succinic acid biosynthesis pathways are summarized, with a focus on the key enzymes and metabolic engineering approaches, which mainly include redirecting carbon flux, balancing NADH/NAD⁺ ratios, and optimizing CO₂ supplementation. Finally, future perspectives on the microbial production of succinic acid are discussed.

Phenazine natural products are a class of colored nitrogen-containing heterocycles produced by various microorganisms mainly originating from marine and terrestrial sources. The tricyclic ring molecules show various chemical structures and the decorating groups dedicate extensive pharmacological activities, including antimicrobial, anticancer, antiparasitic, anti-inflammatory, and insecticidal. These secondary metabolites provide natural materials for screening and developing medicinal compounds in the field of medicine and agriculture due to biological activities. The review presents a systematic summary of the literature on natural phenazines in the past decade, including over 150 compounds, such as hydroxylated, O-methylated, N-methylated, N-oxide, terpenoid, halogenated, glycosylated phenazines, saphenic acid derivatives, and other phenazine derivatives, along with their characterized antimicrobial and anticancer activities. This review may provide guidance for the investigation of phenazines in the future.

Background: Heme is an iron/porphyrin complex compound, widely used in the health care, food, and pharmaceutical industries. It is more advantageous and attractive to develop microbial cell factories to produce heme by fermentation, with lower production costs and environmentally more friendly procedures than those of the traditional extraction based on animal blood. In this study, Bacillus subtilis, a typical industrial model microorganism of food safety grade, was used for the first time as the host to synthesize heme. Results: The heme biosynthetic pathway was engineered as four modules, the endogenous C5 pathway, the heterologous C4 pathway, the uroporphyrinogen (urogen) III synthesis pathway, and the downstream synthesis pathway. Knockout of hemX encoding the negative effector of the concentration of HemA, overexpression of hemA encoding glutamyl-tRNA reductase, and knockout of rocG encoding the major glutamate dehydrogenase in the C5 pathway, resulted in an increase of 427% in heme production. Introduction of the heterologous C4 pathway showed a negligible effect on heme biosynthesis. Overexpression of hemCDB, which encoded hydroxymethylbilane synthase, urogen III synthase, and porphobilinogen synthase participating in the urogen III synthesis pathway, increased heme production by 39%. Knockouts of uroporphyrinogen methyltransferase gene nasF and both heme monooxygenase genes hmoA and hmoB in the downstream synthesis pathway increased heme production by 52%. The engineered B. subtilis produced 248.26 ± 6.97 mg/L of total heme with 221.83 ± 4.71 mg/L of extracellular heme during the fed-batch fermentation in 10 L fermenter. Conclusions: Strengthening endogenous C5 pathway, urogen III synthesis pathway and downstream synthesis pathway promoted the biosynthesis of heme in B. subtilis. The engineered B. subtilis strain has great potential as a microbial cell factory for efficient industrial heme production.

Phycobiliproteins (PBPs) are natural water-soluble pigment proteins, which constitute light-collecting antennae, and function in algae photosynthesis, existing in cyanobacteria, red algae, and cryptomonads. They are special pigment–protein complexes in algae with a unique structure and function. According to their spectral properties, PBPs can be mainly divided into three types: allophycocyanin, phycocyanin, and PE. At present, there are two main sources of PBPs: one is natural PBPs extracted from algae and the other way is recombinant PBPs which are produced in engineered microorganisms. The covalent connection between PBP and streptavidin was realized by gene fusion. The bridge cascade reaction not only improved the sensitivity of PBP as a fluorescent probe but also saved the preparation time of the probe, which expands the application range of PBPs as fluorescent probes. In addition to its function as a light-collecting antenna in photosynthesis, PBPs also have the functions of biological detection, ion detection, and fluorescence imaging. Notably, increasing studies have designed novel PBP-based far-red fluorescent proteins, which enable the tracking of gene expression and cell fate.