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对船舰船体的污损附着，但其防污机制此前尚未明晰。本研究首次针对三种代表性污损生物开展丁烯内酯分子靶点的探究。在对称藤壶（Balanus (=Amphibalanus) amphitrite）中，丁烯内酯可结合至乙酰辅酶A乙酰转移酶1（ACAT1），该酶参与酮体代谢通路；ACAT1的底物与产物均可在丁烯内酯处理条件下促进幼虫附着变态，提示该酶在防污过程中发挥功能性调控作用。在草苔虫（Bugula neritina）中，丁烯内酯可结合至超长链酰基辅酶A脱氢酶（ACADVL）、肌动蛋白以及谷胱甘肽S-转移酶（GSTs），ACADVL是超长链脂肪酸β-氧化通路的首个关键酶；研究发现，替代能源物质（乙酰乙酸与丙酮酸）可在丁烯内酯处理条件下提升幼虫附着率，这一结果佐证了丁烯内酯对该幼虫能量产生核心通路的抑制作用。在海洋弧菌（Vibrio sp. UST020129-010）中，丁烯内酯可结合至琥珀酰辅酶A合成酶β亚基（SCSβ）并抑制细菌生长。乙酰辅酶A乙酰转移酶1、超长链酰基辅酶A脱氢酶以及琥珀酰辅酶A合成酶β亚基均参与能量产生相关的初级代谢过程，上述研究结果表明，丁烯内酯通过干扰靶标生物的初级代谢通路实现其防污功效。