Doing the gene shuffle to close synteny: dynamic assembly of biosynthetic gene clusters.
Doing the gene shuffle to close synteny: dynamic assembly of biosynthetic gene clusters.
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进行基因洗牌以关闭同步：生物合成基因簇的动态组装。
DOI：
10.1111/nph.16631
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Peters RJ
中科院分区：
文献类型：
--
作者：
Peters RJ
在最初的定义中，同线性意味着遗传位点（即基因）的物理共定位，如遗传连锁所证明的那样。这适用于植物似乎已经改组其基因组以组装生物合成基因簇（BGC）用于更专门的代谢的新兴认识（Nutzmann等人，2018年）。然而，这种组装过程并不被很好地理解。事实上，这些BGC可以组装或持续的进化时间尺度尚未得到广泛研究。在这一期的新植物学家刘等。（第100页）1109-1123）已经对菊科中的一种特定类型的BGC进行了这样的分析。具体来说，通过将他们的研究与氧化角鲨烯环化酶结合，作者仅限于研究三萜类化合物的代谢。然而，在此背景下，进行了全面的生物信息学分析，沿着所选BGC的生化表征。结果强烈表明，至少这些菊科三萜类BGC表现出令人惊讶的动态性质，与许多显然已经出现，因为这里检查的组成物种的进化分歧。特别是，虽然同线性是显而易见的，但共簇基因通常是差异排序的，并且尽管通常含有相同酶亚家族的成员，但在遗传学上是不同的。通过重组生物化学表征，显示了两种这样的BGC的不同的三萜类天然产物结果。相比之下，这些BGC中的其他BGC似乎已经持续存在，其中通过一对的生物化学表征证明了它们的正向功能，这意味着保留所得三萜类化合物的一致选择压力，最近至少对于本文检查的BGC对的塔胆醇产物显示出强生物活性（Huang et al.，2019年）。因此，这些BGC很容易组装，但也可以保留，表明不仅仅是基因组不稳定性是其外观的基础。虽然这里报道的结果严格地涉及菊科三萜类BGC，但似乎最有可能的是这种动态基因改组更广泛地适用于植物BGC，提供更广泛的输入。来自相同酶亚家族的基因的重复出现表明，这些提供了在这种BGC组装中已经改组的“三萜类多样化酶的核心调色板”，并且这些提供了“酶家族的天然组合，其可以使用合成生物学来模拟以工程化不同的生物活性分子”。甚至除了这里强调的那些酶家族之外，应该注意的是，其他植物家族可能已经利用不同的酶（亚）家族来
In the original definition, synteny implied physical co-localization of genetic loci–ie, genes–as demonstrated by genetic linkage. This applies to the emerging realization that plants appear to have shuffled their genomes to assemble biosynthetic gene clusters (BGCs) for more specialized metabolism (Nutzmann et al., 2018). However, this assembly process is not well understood. Indeed, the evolutionary timescale over which these BGCs can be assembled, or persist, has not been widely explored. In this issue of New Phytologist Liu et al.(pp. 1109–1123) have carried out such analysis of a particular type of BGC in the Brassicaceae. Specifically, by anchoring their studies with oxidosqualene cyclases, the authors are then limited to examining triterpenoid metabolism. Nevertheless, within this context comprehensive bioinformatic analyses were carried out, along with biochemical characterization of selected BGCs. The results strongly indicate that at least these Brassicaceae triterpenoid BGCs exhibit a surprisingly dynamic nature, with many clearly having arisen since the evolutionary divergence of the constituent species examined here. In particular, while synteny is evident, the co-clustered genes generally are differentially ordered and, although often containing members of the same enzymatic sub-families, phylogenetically distinct. Distinct triterpenoid natural product outcome was shown for two such BGCs by recombinant biochemical characterization. By contrast, others of these BGCs appear to have persisted, with their orthologous function demonstrated by biochemical characterization for one pair, implying consistent selective pressure for retention of the resulting triterpenoids, with strong biological activity recently shown for at least the thalianol product of the pair of BGCs examined here (Huang et al., 2019). Accordingly, these BGCs are readily assembled, yet also can be retained, indicating more than just genomic instability underlies their appearance. While the results reported here strictly pertain to Brassicaceae triterpenoid BGCs, it seems most likely that such dynamic gene shuffling applies to plant BGCs more broadly, providing wider import.As noted by Liu et al., the repeated appearance of genes from the same enzymatic subfamilies indicates that these provide “a core palette of triterpene-diversifying enzymes” that have been shuffled in such BGC assembly, and that these provide “natural combinatorics of enzyme families, which can be mimicked using synthetic biology to engineer diverse bioactive molecules”. Even beyond those enzymatic families highlighted here, it should be noted that other plant families may have utilized distinct enzymatic (sub-) families to
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影响因子：
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