Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Charlotte Auerbach Road, The King's Buildings, Edinburgh, EH9 3FL, United Kingdom.
Department of Chemistry, School of Physical and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, United Kingdom.
Phytochemistry. 2022 Aug;200:113198. doi: 10.1016/j.phytochem.2022.113198. Epub 2022 Apr 18.
Cyanobacteria are an ancient clade of photosynthetic prokaryotes, present in many habitats throughout the world, including water resources. They can present health hazards to humans and animals due to the production of a wide range of toxins (cyanotoxins), including the diaminoacid neurotoxin, 3-N-methyl-2,3-diaminopropanoic acid (β-N-methylaminoalanine, BMAA). Knowledge of the biosynthetic pathway for BMAA, and its role in cyanobacteria, is lacking. Present evidence suggests that BMAA is derived by 3-N methylation of 2,3-diaminopropanoic acid (2,3-DAP) and, although the latter has never been reported in cyanobacteria, there are multiple pathways to its biosynthesis known in other bacteria and in plants. Here, we used bioinformatics analyses to investigate hypotheses concerning 2,3-DAP and BMAA biosynthesis in cyanobacteria. We assessed the potential presence or absence of each enzyme in candidate biosynthetic routes known in Albizia julibrissin, Lathyrus sativus seedlings, Streptomyces, Clostridium, Staphylococcus aureus, Pantoea agglomerans, and Paenibacillus larvae, in 130 cyanobacterial genomes using sequence alignment, profile hidden Markov models, substrate specificity/active site identification and the reconstruction of gene phylogenies. Most enzymes involved in pathways leading to 2,3-DAP in other species were not found in the cyanobacteria analysed. Nevertheless, two species appear to have the genes sbnA and sbnB, responsible for forming the 2,3-DAP constituent in staphyloferrin B, a siderophore from Staphylococcus aureus. It is currently undetermined whether these species are also capable of biosynthesising BMAA. It is possible that, in some cyanobacteria, the formation of 2,3-DAP and/or BMAA is associated with environmental iron-scavenging. The pam gene cluster, responsible for the biosynthesis of the BMAA-containing peptide, paenilamicin, so far appears to be restricted to Paenibacillus larvae. It was not detected in any of the cyanobacterial genomes analysed, nor was it found in 93 other Paenibacillus genomes or in the genomes of two BMAA-producing diatom species. We hypothesise that the presence, in some cyanobacterial species, of the enzymes 2,3-diaminopropionate ammonia-lyase (DAPAL) and reactive intermediate deaminase A (RidA) may explain the failure to detect 2,3-DAP in analytical studies. Overall, the taxonomic distribution of 2,3-DAP and BMAA in cyanobacteria is unclear; there may be multiple and additional routes, and roles, for the biosynthesis of 2,3-DAP and BMAA in these organisms.
蓝藻是一类古老的光合原核生物，存在于世界各地的许多生境中，包括水资源。由于能够产生多种毒素（蓝藻毒素），包括二氨基丙酸神经毒素 3-N-甲基-2,3-二氨基丙酸（β-N-甲基丙氨酸，BMAA），它们可能对人类和动物的健康构成危害。关于 BMAA 的生物合成途径及其在蓝藻中的作用，目前知之甚少。现有证据表明，BMAA 是由 2,3-二氨基丙酸（2,3-DAP）的 3-N 甲基化衍生而来，尽管后者从未在蓝藻中报道过，但在其他细菌和植物中已知有多种途径可以合成它。在这里，我们使用生物信息学分析来研究关于蓝藻中 2,3-DAP 和 BMAA 生物合成的假设。我们使用序列比对、隐马尔可夫模型、底物特异性/活性位点识别以及基因系统发育重建，评估了候选生物合成途径中每种酶在已知的 130 个蓝藻基因组中的存在或缺失情况，这些途径在银合欢、野豌豆幼苗、链霉菌、梭菌、金黄色葡萄球菌、成团泛菌和幼虫芽孢杆菌中。在分析的蓝藻中，没有发现其他物种中导致 2,3-DAP 的途径中涉及的大多数酶。然而，有两种蓝藻似乎具有 sbnA 和 sbnB 基因，这些基因负责形成金黄色葡萄球菌 staphyloferrin B 中 2,3-DAP 成分，staphyloferrin B 是一种来自金黄色葡萄球菌的铁载体。目前还不确定这些物种是否也能够生物合成 BMAA。在某些蓝藻中，2,3-DAP 和/或 BMAA 的形成可能与环境中铁的清除有关。目前看来，负责合成含有 BMAA 的肽 paenilamicin 的 pam 基因簇似乎仅限于幼虫芽孢杆菌。在分析的任何蓝藻基因组中都没有检测到它，也没有在其他 93 个幼虫芽孢杆菌基因组或两个产生 BMAA 的硅藻物种的基因组中检测到它。我们假设，在一些蓝藻物种中，存在 2,3-二氨基丙酸氨裂解酶（DAPAL）和反应性中间物脱氨酶 A（RidA）酶可能解释了在分析研究中未能检测到 2,3-DAP 的原因。总体而言，蓝藻中 2,3-DAP 和 BMAA 的分类分布尚不清楚；这些生物体中 2,3-DAP 和 BMAA 的生物合成可能存在多种和额外的途径和作用。
