52448-17-6Relevant articles and documents
An Obligate Peptidyl Brominase Underlies the Discovery of Highly Distributed Biosynthetic Gene Clusters in Marine Sponge Microbiomes
Nguyen, Nguyet A.,Lin, Zhenjian,Mohanty, Ipsita,Garg, Neha,Schmidt, Eric W.,Agarwal, Vinayak
supporting information, p. 10221 - 10231 (2021/07/26)
Marine sponges are prolific sources of bioactive natural products, several of which are produced by bacteria symbiotically associated with the sponge host. Bacteria-derived natural products, and the specialized bacterial symbionts that synthesize them, are not shared among phylogenetically distant sponge hosts. This is in contrast to nonsymbiotic culturable bacteria in which the conservation of natural products and natural product biosynthetic gene clusters (BGCs) is well established. Here, we demonstrate the widespread conservation of a BGC encoding a cryptic ribosomally synthesized and post-translationally modified peptide (RiPP) in microbiomes of phylogenetically and geographically dispersed sponges from the Pacific and Atlantic oceans. Detection of this BGC was enabled by mining for halogenating enzymes in sponge metagenomes, which, in turn, allowed for the description of a broad-spectrum regiospecific peptidyl tryptophan-6-brominase which possessed no chlorination activity. In addition, we demonstrate the cyclodehydrative installation of azoline heterocycles in proteusin RiPPs. This is the first demonstration of halogenation and cyclodehydration for proteusin RiPPs and the enzymes catalyzing these transformations were found to competently interact with other previously described proteusin substrate peptides. Within a sponge microbiome, many different generalized bacterial taxa harbored this BGC with often more than 50 copies of the BGC detected in individual sponge metagenomes. Moreover, the BGC was found in all sponges queried that possess high diversity microbiomes but it was not detected in other marine invertebrate microbiomes. These data shed light on conservation of cryptic natural product biosynthetic potential in marine sponges that was not detected by traditional natural product-to-BGC (meta)genome mining.
Novel Arylindigoids by Late-Stage Derivatization of Biocatalytically Synthesized Dibromoindigo
Schnepel, Christian,Dodero, Veronica I.,Sewald, Norbert
supporting information, p. 5404 - 5411 (2021/03/03)
Indigoids represent natural product-based compounds applicable as organic semiconductors and photoresponsive materials. Yet modified indigo derivatives are difficult to access by chemical synthesis. A biocatalytic approach applying several consecutive selective C?H functionalizations was developed that selectively provides access to various indigoids: Enzymatic halogenation of l-tryptophan followed by indole generation with tryptophanase yields 5-, 6- and 7-bromoindoles. Subsequent hydroxylation using a flavin monooxygenase furnishes dibromoindigo that is derivatized by acylation. This four-step one-pot cascade gives dibromoindigo in good isolated yields. Moreover, the halogen substituent allows for late-stage diversification by cross-coupling directly performed in the crude mixture, thus enabling synthesis of a small set of 6,6’-diarylindigo derivatives. This chemoenzymatic approach provides a modular platform towards novel indigoids with attractive spectral properties.
Synthesis of the Natural Product Iotrochamide B
Wang,Zhao,Que
, p. 499 - 501 (2019/07/02)
Iotrochamide B is the first cinnamoyl amino acid reported from the marine sponge Iotrochota sp. The total synthesis of the marine indole alkaloid iotrochamide B was achieved by condensation of 6-bromo-L-tryptophan (3) and (Z)-2-methoxy-3-phenylacrylic acid (6). The key step was the synthesis of 6-bromo-L-tryptophan ((S)-3) from racemic N-acetyltryptophan by optical resolution using (S)-(–)-1-phenylethylamine. This work provides an efficient method for future synthesis of iotrochamide B derivatives.
