Dataset Information

Identification, Heterologous Expression, and Characterization of the Tolypodiol Biosynthetic Gene Cluster through an Integrated Approach.

ABSTRACT: Cyanobacteria are tremendous producers of biologically active natural products, including the potent anti-inflammatory compound tolypodiol. However, linking biosynthetic gene clusters with compound production in cyanobacteria has lagged behind that in other bacterial genera. Tolypodiol is a meroterpenoid originally isolated from the cyanobacterium HT-58-2. Here we describe the identification of the tolypodiol biosynthetic gene cluster through heterologous expression in Anabaena and in vitro protein assays of a methyltransferase found in the tolypodiol biosynthetic gene cluster. We have also identified similar biosynthetic gene clusters in cyanobacterial and actinobacterial genomes, suggesting that meroterpenoids with structural similarity to the tolypodiols may be synthesized by other microbes. We also report the identification of two new analogs of tolypodiol that we have identified in both the original and heterologous producer. This work further illustrates the usefulness of Anabaena as a heterologous expression host for cyanobacterial compounds and how integrated approaches can help to link natural product compounds with their producing biosynthetic gene clusters.

SUBMITTER: Back D

PROVIDER: S-EPMC10529828 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification, Heterologous Expression, and Characterization of the Tolypodiol Biosynthetic Gene Cluster through an Integrated Approach.

Back Daniel D O'Donnell Timothy J TJ Axt Kyle K KK Gurr Joshua R JR Vanegas Juan M JM Williams Philip G PG Philmus Benjamin B

ACS chemical biology 20230724 8

Cyanobacteria are tremendous producers of biologically active natural products, including the potent anti-inflammatory compound tolypodiol. However, linking biosynthetic gene clusters with compound production in cyanobacteria has lagged behind that in other bacterial genera. Tolypodiol is a meroterpenoid originally isolated from the cyanobacterium HT-58-2. Here we describe the identification of the tolypodiol biosynthetic gene cluster through heterologous expression in <i>Anabaena</i> and in vit ...[more]

PMID: 37487226

Similar Datasets

Project description:BackgroundThe deep-sea-derived microbe Streptomyces koyangensis SCSIO 5802 produces neoabyssomicins A-B (1-2) and abyssomicins 2 (3) and 4 (4). Neoabyssomicin A (1) augments human immunodeficiency virus-1 (HIV-1) replication whereas abyssomicin 2 (3) selectively reactivates latent HIV and is also active against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Structurally, neoabyssomicins A-B constitute a new subtype within the abyssomicin family and feature unique structural traits characteristic of extremely interesting biosynthetic transformations.ResultsIn this work, the biosynthetic gene cluster (BGC) for the neoabyssomicins and abyssomicins, composed of 28 opening reading frames, was identified in S. koyangensis SCSIO 5802, and its role in neoabyssomicin/abyssomicin biosynthesis was confirmed via gene inactivation and heterologous expression experiments. Bioinformatics and genomics analyses enabled us to propose a biosynthetic pathway for neoabyssomicin/abyssomicin biosynthesis. Similarly, a protective export system by which both types of compounds are secreted from the S. koyangensis producer was identified, as was a four-component ABC transporter-based import system central to neoabyssomicin/abyssomicin biosynthesis. Furthermore, two regulatory genes, abmI and abmH, were unambiguously shown to be positive regulators of neoabyssomicin/abyssomicin biosynthesis. Consistent with their roles as positive regulatory genes, the overexpression of abmI and abmH (independent of each other) was shown to improve neoabyssomicin/abyssomicin titers.ConclusionsThese studies provide new insight into the biosynthesis of the abyssomicin class of natural products, and highlight important exploitable features of its BGC for future efforts. Elucidation of the neoabyssomicin/abyssomicin BGC now enables combinatorial biosynthetic initiatives aimed at improving both the titers and pharmaceutical properties of these important natural products-based drug leads.

Dataset Information

Identification, Heterologous Expression, and Characterization of the Tolypodiol Biosynthetic Gene Cluster through an Integrated Approach.

Publications

Identification, Heterologous Expression, and Characterization of the Tolypodiol Biosynthetic Gene Cluster through an Integrated Approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets