Genetic Organization of Anabaenopeptin and Spumigin Biosynthetic Gene Clusters in the Cyanobacterium Sphaerospermopsis torques-reginae ITEP-024

Abstract

Cyanobacteria produce a broad range of natural products, many of which are potent protease inhibitors. Biosynthetic gene clusters encoding the production of novel protease inhibitors belonging to the spumigin and anabaenopeptin family of nonribosomal peptides were identified in the genome of the bloom-forming cyanobacterium Sphaerospermopsis torques-reginae ITEP-024. The genetic architecture and gene organization of both nonribosomal peptide biosynthetic clusters were compared in parallel with their chemical structure variations obtained by liquid chromatography (LC-MS/MS). The spumigin (spu) and anabaenopeptin (apt) gene clusters are colocated in the genomes of S. torques-reginae ITEP-024 and Nodularia spumigena CCY9414 and separated by a 12 kb region containing genes encoding a patatin-like phospholipase, l-homophenylalanine (l-Hph) biosynthetic enzymes, and four hypothetical proteins. hphABCD gene cluster encoding the production of l-Hph was linked to all eight apt gene clusters investigated here. We suggest that while the HphABCD enzymes are an integral part of the anabaenopeptin biosynthetic pathway, they provide substrates for the biosynthesis of both anabaenopeptins and spumigins. The organization of the spu and apt suggests a plausible model for the biosynthesis of the 4-(4-hydroxyphenyl)-2-acid (Hpoba) precursor of spumigin variants in S. torques-reginae ITEP-024 based on the acceptable substrates of HphABCD enzymes.

Phylogenomic Analysis of Secondary Metabolism in the Toxic Cyanobacterial Genera Anabaena, Dolichospermum and Aphanizomenon

“…A similar gene island consisting of anabaenopeptin, microviridin, and cyanopeptolin can also be found in Planktothrix rubescens NIVA CYA 98 [33]. An anabaenopeptin-spumigin island can be found in Nodularia spumigena CCY9414 and Sphaerospermopsis torques-reginae ITEP-024 [34]. In the latter case, enzymes encoded by the hphABCD genes in apt cluster are used in the supply of homo-amino acids to both spumigin and anabaenopeptin biosynthesis [34].…”

“…An anabaenopeptin-spumigin island can be found in Nodularia spumigena CCY9414 and Sphaerospermopsis torques-reginae ITEP-024 [34]. In the latter case, enzymes encoded by the hphABCD genes in apt cluster are used in the supply of homo-amino acids to both spumigin and anabaenopeptin biosynthesis [34]. HphABCD genes are found also in the spu-apt-mvd gene island of ADA strains NIES-806 and NIES-81 and likely serve the same purpose here.…”

“…Manual curation of cyanobacterial genomes has led to the description of many BGCs involved in the synthesis of natural products [34,[50][51][52]. Nevertheless, most of the natural product BGCs encoded in these genomic sequences have unknown products [53,54].…”

Genomic and Metabolomic Analyses of Natural Products in Nodularia spumigena Isolated from a Shrimp Culture Pond

“…The nonribosomal spu and apt found in the genome of N. spumigena CENA596 showed nearly identical gene organization as in N. spumigena CCY9414 and UHCC 0039 and Sphaerospermopsis torques-reginae ITEP-024. In these strains, spu and apt together are in a genome region separated only by a 12 kbp nucleotide sequence that is believed to encode biosynthetic enzymes of substrates involved in the synthesis of both metabolites [73]. SPU and APT are protease inhibitors [42,43].…”

Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria

“…There has been a recent increase in the number of studies on natural products synthesized by Brazilian cyanobacteria, particularly on toxins and protease inhibitors [43,44,[51][52][53]. However, the diversity of these organisms and their natural products will likely expand as these ecosystems are further explored [54][55][56].…”