Research advances in the biosynthesis of nonribosomal peptides within the bisintercalator family as anticancer drugs
Natural products with the bisintercalator family are a group of C2-symmetric cyclic non-ribosomal peptides produced by actinobacteria,possessing potent antimicrobe,antitumor and other bioactivities.Bisintercalators can be divided into two groups based on the size of their macrocycles:the minor and major scaffold types with eight and ten amino acid residues,respectively.Structure diversity with bisintercalators arises from variations in aromatic heterocycles,amino acid residue identities and quantities,and post-assembly line modifications.The major scaffold type bisintercalators harbor two structurally rigid six-membered nitrogen heterocycle-containing amino acids,which can further undergo oxidative and acylation tailorings.The minor scaffold type bisintercalators seemingly derive their rigidity from disulfide or thioacetal bridges formed by sulfydryls of two cysteines,and the thioacetal bridges allow variable SS-alkyl elongation and conversion of S-alkyl sulfur into sulfoxide moiety.In addition,bisintercalators also exhibit differences in other amino acid identities,which further contribute to their diverse activities,including antimicrobial,antitumor,antifungal,anti-malarial,or antiviral effects.The chemical synthesis of these nonribosomal peptides is complex due to their intricate architectures,making microbial fermentation a more efficient production method.On the other hand,structural optimization can be achieved for bisintercalators through combinatorial and precursor-guided biosynthesis.Therefore,understanding the biosynthetic pathways of bisintercalators is crucial for yield enhancement via the pathway-specific regulation and also offering biocatalytic parts for structural modifications.This knowledge will facilitate future discovery and drug development for this promising natural product family.
NETL
NSTL
万方数据
