Cloning of the Bisucaberin B Biosynthetic Gene Cluster from the Marine Bacterium Tenacibaculum mesophilum, and Heterologous Production of Bisucaberin B

Abstract

The biosynthetic gene cluster for bisucaberin B (1, bsb gene cluster), an N-hydroxy-N-succinyl diamine (HSD)-based siderophore, was cloned from the marine bacterium Tenacibaculum mesophilum, originated from a marine sponge. The bsb gene cluster consists of six open reading frames (ORFs), in contrast to the four ORFs typically seen in biosynthetic gene clusters of the related molecules. Heterologous expression of the key enzyme, BsbD2, which is responsible for the final biosynthetic step of 1 resulted in production of bisucaberin B (1), but not bisucaberin (2) a macrocyclic counterpart of 1. To date, numbers of related enzymes producing macrocyclic analogues have been reported, but this work represents the first example of the HSD-based siderophore biosynthetic enzyme which exclusively produces a linear molecule rather than macrocyclic counterparts.

Discovery and Biosynthesis of Antimicrobial Phenethylamine Alkaloids from the Marine Flavobacterium Tenacibaculum discolor sv11

“…The first one corresponded to a characterized lysine/ornithine decarboxylase involved in the biosynthesis the siderophore bisucaberin. 30 The second one was a putative decarboxylase domain embedded in a large nonribosomal peptide synthetase, therefore likely involved in peptide biosynthesis. The third one was annotated as putative decarboxylase and did not cluster with any other genes.…”

Engineering Siderophore Biosynthesis and Regulation Pathways to Increase Diversity and Availability

“…In addition, a part of or entire BGCs have also been reconstituted in a heterologous host [ 90 ], allowing for characterization of the cluster and the siderophore produced. In this case, the host offers the opportunity to be used as a platform to test gene clusters potentially involved in siderophore synthesis [ 91 ]. Such an approach thus facilitates the design of diversified siderophores using engineering strategies [ 77 ].…”

“…to test gene clusters potentially involved in siderophore synthesis [91]. Such an approach thus facilitates the design of diversified siderophores using engineering strategies [77].…”

Microbial Catalysis for CO2Sequestration: A Geobiological Approach

“…Siderophore synthesis pathways have been identified in many organisms through both experiments and bioinformatics (Hider and Kong 2010;Garber et al 2020Garber et al , 2021. Several pathways have been expressed and further engineered in the model organism Escherichia coli, with the goal of producing siderophores as therapeutic antibiotics (Fujita and Sakai 2013;Fujita et al 2018). To our knowledge, there have been limited efforts to enhance the production of endogenous siderophores, to date.…”