Abstract

Tolyporphins A–R are unusual tetrapyrrole macrocycles produced by the non-axenic filamentous cyanobacterium HT-58-2. A putative biosynthetic gene cluster for biosynthesis of tolyporphins (here termed BGC-1) was previously identified in the genome of HT-58-2. Here, homology searching of BGC-1 in HT-58-2 led to identification of similar BGCs in seven other filamentous cyanobacteria, including strains Nostoc sp. 106C, Nostoc sp. RF31YmG, Nostoc sp. FACHB-892, Brasilonema octagenarum UFV-OR1, Brasilonema octagenarum UFV-E1, Brasilonema sennae CENA114 and Oculatella sp. LEGE 06141, suggesting their potential for tolyporphins production. A similar gene cluster (BGC-2) also was identified unexpectedly in HT-58-2. Tolyporphins BGCs were not identified in unicellular cyanobacteria. Phylogenetic analysis based on 16S rRNA and a common component of the BGCs, TolD, points to a close evolutionary history between each strain and their respective tolyporphins BGC. Though identified with putative tolyporphins BGCs, examination of pigments extracted from three cyanobacteria has not revealed the presence of tolyporphins. Overall, the identification of BGCs and potential producers of tolyporphins presents a collection of candidate cyanobacteria for genetic and biochemical analysis pertaining to these unusual tetrapyrrole macrocycles.

Highlights

  • IntroductionThe agent, a glycosylated tetrapyrrole macrocycle termed tolyporphin A, reversed multidrug resistance in SKVLB1 carcinoma cells in vitro [9]

  • aminolevulinic acid (ALA) is converted to uroporphyrinogen III that serves as the universal branch-point for tetrapyrrole biosynthesis (Figure 2) [26,27]

  • This study has revealed seven new potential producers of tolyporphins based on protein sequences of BGC-1 of cyanobacterium HT-58-2 by the combination of genome mining and comparative genomics analysis

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Summary

Introduction

The agent, a glycosylated tetrapyrrole macrocycle termed tolyporphin A, reversed multidrug resistance in SKVLB1 carcinoma cells in vitro [9]

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