Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology & School of Life Sciences, South China Normal University, Guangzhou, China.
Guangmeiyuan R&D Center, Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, South China Normal University, Meizhou, China.
BMC Biol. 2024 May 13;22(1):111. doi: 10.1186/s12915-024-01910-4.
Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.
In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for the biosynthesis of JHB3 and JH III in D. melanogaster. The Cyp6g2 is predominantly expressed in the corpus allatum (CA), concurring with the expression pattern of jhamt, another well-studied gene that is crucial in the last steps of JH biosynthesis. Mutation in Cyp6g2 leads to severe disruptions in larval-pupal metamorphosis and exhibits reproductive deficiencies, exceeding those seen in jhamt mutants. Notably, Cyp6g2::jhamt double mutants all died at the pupal stage but could be rescued through the topical application of JH analogs. JH titer analyses revealed that both Cyp6g2 mutant and jhamt mutant lacking JHB3 and JH III, while overexpression of Cyp6g2 or jhamt caused a significant increase in JHB3 and JH III titer.
These findings collectively established that Cyp6g2 as the major JH epoxidase in the higher dipterans and laid the groundwork for the further understanding of JH biosynthesis. Moreover, these findings pave the way for developing specific Cyp6g2 inhibitors as insect growth regulators or insecticides.
保幼激素（JH）在昆虫的发育和生殖中起着至关重要的作用。最常见的 JH 形式是 JH III，它是通过 CYP15 酶的环氧化作用从 MF 衍生而来的。然而，在高等双翅目昆虫中，如果蝇，检测到的 JH 主要是 JHB3 的双环氧化物形式。此外，这些高等双翅目昆虫已经从其基因组中丢失了 CYP15 基因。因此，高等双翅目昆虫 JH 生物合成途径中的 P450 环氧化酶的身份仍然未知。
在这项研究中，我们表明 Cyp6g2 是主要的 JH 环氧化酶，负责果蝇中 JHB3 和 JH III 的生物合成。Cyp6g2 在脑下垂体（CA）中表达丰富，与另一个在 JH 生物合成最后步骤中至关重要的基因 jhamt 的表达模式一致。Cyp6g2 突变导致幼虫-蛹变态严重中断，并表现出生殖缺陷，超过了 jhamt 突变体的缺陷。值得注意的是，Cyp6g2::jhamt 双突变体都在蛹期死亡，但可以通过涂抹 JH 类似物来挽救。JH 滴度分析表明，Cyp6g2 突变体和 jhamt 突变体都缺乏 JHB3 和 JH III，而 Cyp6g2 或 jhamt 的过表达导致 JHB3 和 JH III 滴度显著增加。
这些发现共同确立了 Cyp6g2 是高等双翅目昆虫中主要的 JH 环氧化酶，并为进一步了解 JH 生物合成奠定了基础。此外，这些发现为开发特定的 Cyp6g2 抑制剂作为昆虫生长调节剂或杀虫剂铺平了道路。
