Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.

The nonribosomal peptide synthetase (NRPS) is a highly precise molecular assembly machinery for synthesizing structurally diverse peptides, which have broad medicinal applications. Withinthe NRPS, the condensation (C) domain is a core catalytic domain responsible for the formation of amide bonds between individual monomer residues during peptide elongation. This review summarizes various aspects of the C domain, including its structural characteristics, catalytic mechanisms, substrate specificity, substrate gating function, and auxiliary functions. Moreover, through case analyses of the NRPS engineering targeting the C domains, the vast potential of the C domain in the combinatorial biosynthesis of peptide natural product derivatives is demonstrated.

Nonribosomal peptides (NRPs) are biosynthesized by nonribosomal peptide synthetases (NRPSs) and are widely distributed in both terrestrial and marine organisms. Many NRPs and their analogs are biologically active and serve as therapeutic agents. The adenylation (A) domain is a key catalytic domain that primarily controls the sequence of a product during the assembling of NRPs and thus plays a predominant role in the structural diversity of NRPs. Engineering of the A domain to alter substrate specificity is a potential strategy for obtaining novel NRPs for pharmaceutical studies. On the basis of introducing the catalytic mechanism and multiple functions of the A domains, this article systematically describes several representative NRPS engineering strategies targeting the A domain, including mutagenesis of substrate-specificity codes, substitution of condensation-adenylation bidomains, the entire A domain or its subdomains, domain insertion, and whole-module rearrangements.

Dunaliella salina is an important source of natural β-carotene (containing 9-cis and all trans isomers) for industrial production. The phytohormone salicylic acid (SA) has been proven to have impacts on the stress resistance of higher plants, but research on microalgae is currently unclear. In this study, the effects of SA on the growth, biochemical composition, antioxidant enzyme activity, key enzymes of β-carotene synthesis, and cis-and trans-isomers of β-carotene in D. salina under different salt concentrations were investigated. The results were shown that at concentrations of 1.5, 2, and 2.5 M NaCl, the antioxidant enzyme activity and key enzymes for β-carotene synthesis in algal cells were significantly increased, but the content and proportion of 9-cis isomer in β-carotene isomers decreased. The addition of SA significantly increased the growth and antioxidant enzyme (SOD, MDA) activity, as well as the synthesis of key enzyme phytoene synthase (PSY), phytoene desaturase (PDS), and lycopene β cyclase (LCYB) of D. salina under high-salinity conditions. It is worth noting that under the treatment of SA, the proportion of 9-cis isomer in the three salt concentrations (1.5, 2, 2.5 M NaCl) significantly increased by 32.09%, 20.30%, and 11.32%, respectively. Moreover, SA can not only improve the salt tolerance of D. salina, but also increase the proportion of 9-cis isomer, with higher physiological activity in β-carotene, thereby enhancing the application value of D. salina.

In recent years, the role of lectins in the feed selection of bivalve has become hot research topic. Manila clam Ruditapes philippinarum is a species of marine bivalve with important economic value. A new C-type lectin (Rpcl) from the clam was obtained and its potential role in feeding and feed selection was studied. Rpcl cDNA was 929 bp in length and had 720 bp of open reading frame. Rpcl encoded 235 amino acids, comprising a carbohydrate recognition domain (CRD) as well as an N-terminal signal peptide. Rpcl contained a conserved CRD disulfide bond including five cysteine residues (Cys¹²⁵, Cys¹⁴², Cys²¹³, Cys²¹⁹, and Cys²³⁷) and the QPN motif (GLN²⁰⁴-PRO²⁰⁵-ASN²⁰⁶). Phylogenetic analysis revealed that the amino acid sequence of Rpcl was closely related to that of Vpclec-1 from R. philippinarum and C-type lectin from Mercenaria. The qPCR analysis indicated that Rpcl expression was observed in all examined tissues and was the highest in gills followed by in the hepatopancreas, and to a lesser extent in the mantle and lip. The in vitro agglutination experiments showed that, the purified Rpcl protein could selectively agglutinate with different microalgae. The strongest agglutinating effect with Chlorella sp. was observed, followed by Karlodinium veneficum and Chaetoceros debilis Cleve. No agglutination with Prorocentrum minimum was observed. In the feeding experiment, compared with that of the starvation group, Rpcl expression in the lip and gill of the clam fed with C. debilis and K. veneficum showed a significant upward trend with the change of time. In addition, it was found that the changes in the expression of the Rpcl gene in the gill and lip, the main feeding tissues, were consistent with the slope of the decrease in the number of algal cells in the water body. In summary, the structure of a new C-type lectin (Rpcl) was reported in this study and its correlation with the feeding and feed selection in R. philippinarum was confirmed.

TRNA methylations, including base modification and 2’-O-methylation of ribose moiety, play critical roles in the structural stabilization of tRNAs and the fidelity and efficiency of protein translation. These modifications are catalyzed by tRNA methyltransferases (TRMs). Some of the TRMs from yeast can fully function only by a single subunit. In this study, after performing the primary bioinformatic analyses, the progress of the studies of yeast single-subunit TRMs, as well as the studies of their homologues from yeast and other types of eukaryotes and the corresponding TRMs from other types of organisms was systematically reviewed, which will facilitate the understanding of the evolutionary origin of functional diversity of eukaryotic single-subunit TRM.