Engineering Microbiology最新文献

The recently discovered type IX secretion system (T9SS) is limited to the Bacteroidetes phylum. Cytophaga hutchinsonii, a member of the Bacteroidetes phylum widely spread in soil, has complete orthologs of T9SS components and many T9SS substrates. C. hutchinsonii can efficiently degrade crystalline cellulose using a novel strategy, in which bacterial cells must be in direct contact with cellulose. It can rapidly glide over surfaces via unclear mechanisms. Studies have shown that T9SS plays an important role in cellulose degradation, gliding motility, and ion assimilation in C. hutchinsonii. As reported recently, T9SS substrates are N- or O-glycosylated at their C-terminal domains (CTDs), with N-glycosylation being related to the translocation and outer membrane anchoring of these proteins. These findings have deepened our understanding of T9SS in C. hutchinsonii. In this review, we focused on the research progress on diverse substrates and functions of T9SS in C. hutchinsonii and the glycosylation of its substrates. A model of T9SS functions and the glycosylation of its substrates was proposed.

Triterpenes are derived from squalene or oxidosqualene. However, a new class of triterpenes derived from hexaprenyl pyrophosphate has been recently discovered, formed by a new family of chimeric class I triterpene synthases. The cyclization mechanisms of triterpenes were elucidated by isotopic labeling and protein structural analyses, which helps understand the biosynthesis of triterpenes in nature.

Peptaibols are a large family of linear, amphipathic polypeptides consisting of 5-20 amino acid residues generated from the fungal nonribosomal peptide synthetase (NRPS) pathway. With a relatively high content of non-proteinogenic amino acids such as α-aminoisobutyrate (Aib) and isovaline (Iva) in the skeleton, peptaibols exhibit a wide range of biological activities, including anti-microbial, cytotoxic, and neuroleptic effects. With five peptaibols brought to market for use as biocontrol agents, this class of peptides has received increasing attention from both biochemists and pharmacologists. In this review, we summarized the progress made in structural characterization, elucidation of biosynthetic pathways, and investigation of biosynthesis elucidation and bioactivities, to promote further efforts to develop peptaibols as pharmaceuticals.

The development of drug delivery vehicles is in significant demand in the context of precision medicine. With the development of synthetic biology, the use of genetically engineered bacteria as drug delivery vectors has attracted more and more attention. Herein, we reviewed the research advances in bioengineered bacteria as drug carriers, with emphasis on the synthetic biology strategies for modifying these bacteria, including the targeted realization method of engineered bacteria, the designing scheme of genetic circuits, and the release pathways of therapeutic compounds. Based on this, the essential components, design principles, and health concerns of engineering bacteria as drug carriers and the development prospects in this field have been discussed.

Copper-radical oxidases (CROs) catalyze the two-electron oxidation of a large number of primary alcohols including carbohydrates, polyols and benzylic alcohols as well as aldehydes and α-hydroxy-carbonyl compounds while reducing molecular oxygen to hydrogen peroxide. Initially, CROs like galactose oxidase and glyoxal oxidase were identified only in fungal secretomes. Since the last decade, their representatives have also been identified in some bacteria. CROs are grouped in the AA5 family of “auxiliary activities” in the database of Carbohydrate-Active enzymes. Despite low overall sequence similarity and different substrate specificities, sequence alignments and the solved crystal structures revealed a conserved architecture of the active sites in all CROs, with a mononuclear copper ion coordinated to an axial tyrosine, two histidines, and a cross-linked cysteine-tyrosyl radical cofactor. This unique post-translationally modified protein cofactor has attracted much attention in the past, which resulted in a large number of reports that shed light on key steps of the catalytic cycle and physico-chemical properties of CROs. Thanks to their broad substrate spectrum accompanied by the only need for molecular oxygen for catalysis, CROs since recently experience a renaissance and have been applied in various biocatalytic processes. This review provides an overview of the structural features, catalytic mechanism and substrates of CROs, presents an update on the engineering of these enzymes to improve their expression in recombinant hosts and to enhance their activity, and describes their potential fields of biotechnological application.

Natural occurring aromatic polyketides from actinomycetes indicate a structurally and functionally diverse family of polycyclic polyphenols. Some of them are consequently suggested as lead structures for drug development. Among them, rubromycins are derived from a single C26 polyketide chain and exhibit an unusual bisbenzannulated [5,6]-spiroketal system that connects a highly oxygenated naphthazarin motif to an isocoumarin unit. This type of biosynthetically elusive polycyclic polyketides has shown promising pharmacological activities, including antimicrobial, anticancer, and enzyme inhibition activity. The unique structures, intriguing biosynthesis, and marked bioactivities of rubromycins have drawn considerable attention from several chemists and biologists. This review covers the isolation, characterization, biosynthesis, and biological studies of these structurally diverse and complex rubromycins.