Butenolide Inhibits Marine Fouling by Altering the Primary Metabolism of Three Target Organisms

Butenolide is a very promising antifouling compound that
inhibits
ship hull fouling by a variety of marine organisms, but its antifouling
mechanism was previously unknown. Here we report the first study of
butenolide’s molecular targets in three representative fouling
organisms. In the barnacle Balanus (=Amphibalanus) amphitrite, butenolide bound to acetyl-CoA acetyltransferase 1 (ACAT1), which
is involved in ketone body metabolism. Both the substrate and the
product of ACAT1 increased larval settlement under butenolide treatment,
suggesting its functional involvement. In the bryozoan Bugula
neritina, butenolide bound to very long chain acyl-CoA dehydrogenase
(ACADVL), actin, and glutathione S-transferases (GSTs).
ACADVL is the first enzyme in the very long chain fatty acid β-oxidation
pathway. The inhibition of this primary pathway for energy production
in larvae by butenolide was supported by the finding that alternative
energy sources (acetoacetate and pyruvate) increased larval attachment
under butenolide treatment. In marine bacterium Vibrio sp. UST020129-010, butenolide bound to succinyl-CoA synthetase β
subunit (SCSβ) and inhibited bacterial growth. ACAT1, ACADVL,
and SCSβ are all involved in primary metabolism for energy production.
These findings suggest that butenolide inhibits fouling by influencing
the primary metabolism of target organisms.

丁烯内酯（butenolide）是一种极具应用前景的防污化合物，可抑制多种海洋生物造成的船体污损，但此前其防污机制尚未明确。本文首次针对三种典型污损生物中的丁烯内酯分子靶标开展研究。
在纹藤壶（Balanus (=Amphibalanus) amphitrite）中，丁烯内酯可与乙酰辅酶A乙酰转移酶1（ACAT1）结合，该酶参与酮体代谢过程。在丁烯内酯处理条件下，ACAT1的底物与产物均能促进幼虫附着，提示该酶在防污过程中发挥了功能性作用。
在膜孔苔虫（Bugula neritina）中，丁烯内酯可与极长链酰基辅酶A脱氢酶（ACADVL）、肌动蛋白（actin）以及谷胱甘肽S-转移酶（GSTs）结合。ACADVL是极长链脂肪酸β氧化通路中的首个关键酶。研究发现，在丁烯内酯处理条件下，替代能源（乙酰乙酸与丙酮酸）可促进幼虫附着，这佐证了丁烯内酯会抑制幼虫能量产生的核心通路。
在海洋弧菌（Vibrio sp.）UST020129-010中，丁烯内酯可与琥珀酰辅酶A合成酶β亚基（SCSβ）结合并抑制细菌生长。
ACAT1、ACADVL与SCSβ均参与生物体能量产生相关的初级代谢过程。上述研究结果表明，丁烯内酯通过影响靶标生物的初级代谢通路实现防污效果。