Prymnesium parvum are harmful haptophyte algae that cause massive environmental fish kills. Their polyketide polyether toxins, the prymnesins, are among the largest nonpolymeric compounds in nature and have biosynthetic origins that have remained enigmatic for more than 40 years. In this work, we report the “PKZILLAs,” massive P. parvum polyketide synthase (PKS) genes that have evaded previous detection. PKZILLA-1 and -2 encode giant protein products of 4.7 and 3.2 megadaltons that have 140 and 99 enzyme domains. Their predicted polyene product matches the proposed pre-prymnesin precursor of the 90-carbon–backbone A-type prymnesins. We further characterize the variant PKZILLA-B1, which is responsible for the shorter B-type analog prymnesin-B1, from P. parvum RCC3426 and thus establish a general model of haptophyte polyether biosynthetic logic. This work expands expectations of genetic and enzymatic size limits in biology.

中文翻译：

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巨型海洋聚醚毒素生物合成中的巨型聚酮合酶


Prymnesium parvum 是一种有害的触生藻类，会导致大量环境鱼类死亡。它们的聚酮化合物聚醚毒素，即原草菌素，是自然界中最大的非聚合化合物之一，其生物合成起源在 40 多年来一直是个谜。在这项工作中，我们报告了“PKZILLAs”，这是一种逃避了先前检测的大量 P. parvum 聚酮合酶 (PKS) 基因。 PKZILLA-1和-2编码4.7和3.2兆道尔顿的巨型蛋白质产物，具有140和99个酶结构域。他们预测的多烯产物与所提出的 90-碳主链 A 型 prymnesin 的前 prymnesin 前体相匹配。我们进一步表征了来自 P. parvum RCC3426 的变体 PKZILLA-B1，它负责较短的 B 型类似物 prymnesin-B1，从而建立了触生菌聚醚生物合成逻辑的通用模型。这项工作扩大了生物学中对遗传和酶大小限制的期望。